摘要
采用体外转录的方法,分别在SP6和T7 RNA聚合酶的作用下合成地高辛(DIG)标记的Cdc25A, Cdc25B, Sox2和Mnb/Dyrk RNA探针。通过全胚胎原位杂交的方法检测早期鸡胚中上述四种基因mRNA的表达模式。结果表明,四种基因mRNA的表达模式是部分重叠或互补的,大部分表达于整个中枢神经系统(CNS),但也有表达于体节和肢芽。在特异的区域,四种基因的mRNA丰度是存在差异的。在鸡胚早期不同发育阶段,四种基因的表达模式支持了它们可能在早期的鸡胚发育中具有重要的调节功能,而且它们之间具有一定的相互调控作用。
试验ⅠCdc25ARNA探针的制备本试验应用RT-PCR方法从鸡胚中扩增Cdc25A的基因片段,通过T-A克隆将其连接于pGM-T质粒载体中构成Cdc25A/pGM-T重组质粒。并将重组质粒转化入大肠杆菌DH5α株感受态细胞中扩增,经挑取阳性克隆进行扩增培养、小量提取质粒,再根据pGM-T的多克隆酶切位点,进行酶切鉴定,然后经测序验证。测序正确后,将阳性株扩增后提取的质粒分别用限制性内切酶NcoⅠ和SpeⅠ进行酶切,使其完全线性化。回收酶切片段,作为合成正、反义RNA探针的模板。分别利用pGM-T中T7和SP6的RNA聚合酶的启动子,在RNA聚合酶的作用下,以线性化的Cdc25A/pGM-T为模板,按Roche地高辛标记试剂盒说明书,利用试剂盒中含有的DIG-dUTP底物混合物,分别用Sp6和T7转录酶进行体外转录,成功转录得到长度为183nt的正、反义DIG标记的RNA探针,为后续的原位杂交试验做好了探针的准备。
试验ⅡCdc25A mRNA在早期鸡胚中的分布本试验通过全胚胎原位杂交的方法,使用Cdc25A RNA探针检测其mRNA在早期鸡胚中的分布。结果表明,在9HH(Hamburger and Hamilton)阶段,脑部的杂交信号相对于后期阶段(10,11HH)不强,但中部神经管杂交信号相对于后期阶段较强。后部神经沟,尾部神经板杂交信号此时较强。体节部位信号最弱。在10HH阶段,脑部杂交信号此时很强,但中部神经管杂交信号很弱。体节处的杂交信号也较少。后部神经沟,尾部神经板杂交信号依然较强。在11HH阶段,头部区域的杂交信号仍然最强,中部神经管杂交信号有所加强,后部神经沟,尾部神经板杂交信号有所减弱。此时,在心原基中未见杂交信号。这些结果说明,Cdc25A mRNA的表达模式与增殖中的神经上皮分布区域基本一致。
试验ⅢCdc25B RNA探针的制备及其mRNA在早期鸡胚神经管、体节和肢芽中的分布本试验使用分子克隆的方法获得特异性Cdc25B基因目的片段,以线性化的Cdc25B/pGM-T重组质粒为模板,应用体外转录的方法合成长度为575nt的正、反义地高辛标记的Cdc25B RNA探针。通过全胚胎原位杂交方法,用体外转录的Cdc25BRNA探针探查Cdc25B mRNA在早期鸡胚中的动态表达模式。结果表明,在5HH阶段,Cdc25B原位杂交信号在整个胚胎中分布是微弱的,特别是在头部区域,但在亨氏节(Hensen's node)中杂交信号可见。此时,Cdc25B杂交信号不对称地分布在亨氏节的左侧。在6HH阶段,脑部杂交信号已经清晰可见。杂交信号在亨氏节和原条两侧是不对称的。到了8ˉHH期,脑部杂交信号很强,并且在神经褶中Cdc25B原位杂交信号也较强。此时,神经褶两侧杂交信号分布是对称的,但亨氏节两侧信号仍然是不对称的。在全胚胎原位杂交的横断切片中,Cdc25B原位杂交信号分布在底板。在即将封闭的神经管中,杂交信号呈现出腹背递减的浓度梯度,而且,在大部分尾部神经上皮中缺乏杂交信号。体节中的杂交信号很弱。直到8HH阶段,Cdc25B原位杂交信号在脑部很强。在体节中的杂交信号也较强。从Cdc25B原位杂交的横断切片来看,在8HH阶段,杂交信号在神经管和神经沟两侧是对称的,但在即将封闭的神经管和神经沟中,杂交信号仍然呈现出腹背递减的浓度梯度。从9ˉ到10HH阶段,杂交信号分布于CNS,包括脑部,神经管和神经沟。特别是,脑部的杂交信号很强,但是在10HH阶段,在尾部神经板中没有杂交信号。此外,体节中的信号较强。在12HH阶段,Cdc25B原位杂交信号分布于CNS,特别是脑部比先前发育阶段信号更强。此时,体节中的杂交信号较强。在三天的鸡胚(18HH阶段)切片中,Cdc25B原位杂交信号仍然分布在神经管的腹部区域。体节中信号很强。同时在肢芽的顶端,即AER区域,Cdc25B原位杂交信号很强。在后期的23HH阶段,杂交信号广泛分布于发育中的脊髓,主要分布在腹部区域,并且在腹部区域的外侧缘检测到强烈的信号。此时,体节中信号也较强。然而,自始至终,在早期鸡胚不同发育阶段,脊索都是阴性的。所有这些结果说明,在早期鸡胚不同发育阶段,Cdc25B mRNA主要分布于CNS,在体节和肢芽中也有不同程度地分布。但是,大部分尾部神经上皮中缺乏Cdc25B mRNA分布。
试验ⅣSox2 RNA探针的制备及其mRNA在早期鸡胚中的原位杂交检测本试验应用体外转录的方法合成正、反义地高辛标记的Sox2 RNA探针。通过全胚胎原位杂交方法,使用体外转录的探针检测Sox2 mRNA在10HH阶段鸡胚中的表达情况。结果表明,Sox2原位杂交信号沿着CNS区域分布。杂交信号在脑部很强。中部神经管的杂交信号较弱。然而,在尾部神经板杂交信号较强。此外,在体节中并未见到杂交信号。这些结果说明,Sox2 mRNA主要分布在CNS未成熟的神经上皮中。Sox2 mRNA与Cdc25A mRNA在早期鸡胚中的分布模式具有相似性。
试验ⅤMnb/Dyrk RNA探针的制备及其全鸡胚原位杂交反应本试验应用体外转录的方法合成正、反义地高辛标记Mnb/Dyrk的RNA探针。通过全胚胎原位杂交方法,用体外转录的RNA探针检测了10HH阶段的鸡胚Mnb/Dyrk mRNA的表达模式。结果表明,Mnb/Dyrk原位杂交信号在CNS中很强。在封闭的神经管中可检测到杂交信号,包括将来发育为前脑,中脑和菱脑的区域,以及脊髓。在头部有很强的杂交信号。尾部神经板区域杂交信号很弱。此外,在体节中杂交信号很弱。这些结果说明,Mnb/Dyrk mRNA主要分布于CNS中。Mnb/Dyrk mRNA在早期鸡胚中的分布与Cdc25B是相似的。
The sense and antisense digoxigenin-labeled RNA probes of Cdc25A, Cdc25B, Sox2 and Mnb/Dyrk four genes were produced by using SP6 and T7 RNA polymerases respectively and in vitro transcription. Expression patterns of four genes were detected by in situ hybridization in various developmental HH(Hamburger and Hamilton) stages of the early chick embryo. The results indicate that expression patterns of four genes were similar or complementary. Four genes mRNA was mostly restricted to the entire CNS (central nervous system). All of them have become confined to an identical region, neural tube, neural groove or caudal neural plate, corresponding to spinal cord. But there was some distinction in specific region or in concentration, for example in somites. Four genes mRNA was overlapping in the head region. Cdc25A and Cdc25B mRNA was complementary in CNS except head. The overlap in expression in the same developmental stage in CNS suggests that four genes may be functional similar or relation in CNS development. Expression patterns of four genes support specific roles of these regulators in the developing CNS.
ExperimentⅠPreparation of chicken Cdc25A RNA probe To study the distribution of Cdc25A mRNA in early chicken embryo, the sense and anti-sense digoxigenin (DIG) labeled RNA probe were prepared. The fragment of Cdc25A gene was obtained by RT-PCR through total RNA of chicken embryos. Amplified cDNA fragment was subcloned into pGM-T vector, and the plasmid was transformed into E. coli DH5a and chosen by "white-blue plaque selection". The recombinant plasmid was identified by EcoR I restriction enzyme digestion and sequencing, then Cdc25A/pGM-T vector was linearized with the restriction enzyme of Nco I and Spe I respectively. The sense and anti-sense DIG labeled RNA probe were producted by SP6 and T7 RNA polymerase respectively and transcription in vitro according to the protocol of "DIG RNA Labeling Kit (SP6/T7)".
ExperimentⅡCdc25A mRNA was detected in chicken embryos by whole mount in situ hybridization histochemistry The distribution of Cdc25A mRNA in chicken embryo was examined by whole mount in situ hybridization histochemistry (ISHH). In stage 9HH, Cdc25A mRNA was weak in rostral head and little in the somites. But there was fruitful in the neural tube, neural groove and neural plate. In stage 10HH, Cdc25A mRNA expression was most redundant in rostral head fold. The caudal neural plate was fairly plentiful, but the middle neural tube was little. In addition, the mRNA was weak in somites. In stage 11HH, Cdc25A mRNA expression was most redundant in rostral head fold. The middle neural tube had more mRNA than prior stages. The mRNA was weak in neural groove and caudal neural plate. In addition, no Cdc25A mRNA was detected in heat primordium. The distribution of Cdc25A mRNA was in neuroepithelium.
ExperimentⅢPreparation of chicken Cdc25B RNA probe and its detection in neural tube、somites and limb bud in chicken embryos by whole mount in situ hybridization histochemistry In order to study the distributions of Cdc25B mRNA in chicken embryos, the sense and anti-sense digoxigenin (DIG) labeled RNA probes were prepared. The distributions of Cdc25B mRNA in the embryos were examined by means of whole mount in situ hybridization histochemistry (ISHH). In stage 5HH, Cdc25B mRNA was only emerged in the left of Hensen's node. In stage 6HH, Cdc25B mRNA was visible in head fold; distribution of Cdc25B mRNA was asymmetrical in Hensen's node. In stage 8-HH embryos, Cdc25B mRNA was conspicuous in the rostral head fold, and the mRNA of Cdc25B was very abundant in the neural fold; the staining of the neural fold was symmetrical, but that of Hensen's node was still asymmetrical. Cdc25B transcripts were present on both sides of the floor plate, displayed a ventro-dorsally decreasing gradient in the closing neural tube. The somites were faintly visible. In stage 8HH, the transcripts of Cdc25B were plentiful in the head fold. The somites were made clearly visible by staining. From stage 9- to 10HH, mRNA of Cdc25B was confined to the CNS, including the brain, neural tube, and neural groove. But in stage 10HH, the staining was scarce in the caudal neural plate. Cdc25B mRNA was conspicuous in the somites. In stage 12HH, the staining was stronger than in the previous stages in the CNS, especially in the head fold. Cdc25B mRNA was obvious in the somites. In stage 18HH embryos, Cdc25B was found to be still expressed in a discrete ventral domain in the neural tube. Cdc25B mRNA was detected in the tip of the limb bud. In stage 23HH embryos, Cdc25B was broadly expressed in the developing spinal cord. In general, expression patterns of Cdc25B were restricted in the CNS, somites and the tip of the limb bud in different HH stages during embryo development.
ExperimentⅣDistribution of Sox2 in CNS of chicken embryo by whole mount in situ hybridization In order to study the distributions of Sox2 mRNA in chicken embryos, the sense and anti-sense digoxigenin (DIG) labeled RNA probes were prepared. The distributions of Sox2 mRNA in the stage 10HH in chicken embryos were examined by means of whole mount in situ hybridization histochemistry (ISHH). Sox2 was predominantly expressed in the immature neural epithelium of the entire CNS. Sox2 express in a band along the length of most of the CNS and in all compartments of the brain. Sox2 mRNA expression was redundant in rostral head fold according to the staining. The middle neural tube was weak of expression. The caudal neural plate was fairly plentiful. In addition, Sox2 expression was not visible in somites.In general, Sox2 mRNA was detected in the proliferative neural epithelium. The distribution of Sox2 and Cdc25A mRNA was similar in stage 10HH in chicken embryos.
Experiment V Distribution of Mnb/Dyrk in CNS of chicken embryo by whole mount in situ hybridization In order to study the distributions of Mnb/Dyrk mRNA in chicken embryos, the sense and anti-sense digoxigenin (DIG) labeled RNA probes were prepared. The distributions of Mnb/Dyrk mRNA in the stage 10HH in chicken embryos were examined by means of whole mount in situ hybridization histochemistry (ISHH). Mnb/Dyrk mRNA was considerable in CNS. In HH stage 10, Mnb/Dyrk mRNA can be detected at different levels of the neural tube:the prospective prosencephalon, mesencephalon, rhombencephalon, and spinal cord. The mRNA was redundant in rostral head fold. But it was weak in caudal neural plate. Moreover, Mnb/Dyrk mRNA was very poor in somites. The distribution of Mnb/Dyrk and Cdc25B mRNA was similar in stage 10HH in chicken embryos.
引文
蔡文琴.发育神经生物学[M].北京：科学出版社,2007,93-144.
丁斐.神经生物学[M].北京：科学出版社,2007,25-88.
樊启昶,白书农.发育生物学原理[M].北京：高等教育出版社,2002,74-87.
范小棠Noggin基因与中枢神经系统发育的研究进展[J].生理科学进展,2006,37(2)：121-24.
Altmann CR, Brivanlou AH. Neural patterning in the vertebrate embryo[J]. Int Rev Cytol,2001,203: 447-82.
Ang SL, Jin O, Rhinn M, et al. A targeted mouse Otx2 mutation leads to severe defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain[J]. Development,1996,122(1): 243-52.
Bardine N, Donow C, Korte B, et al. Two Hoxc6 transcripts are differentially expressed and regulate primary neurogenesis in Xenopus laevis[J]. Dev Dyn,2009,238(3):755-65.
Graham A, Lumsden A. Interactions between rhombomeres modulate Krox-20 and follistatin expression in the chick embryo hindbrain[J]. Development,1996,122(2):473-80.
Joyner AL. Engrailed. Wnt and Pax genes regulate midbrain--hindbrain development[J]. Trends Genet, 1996,12(1):15-20.
Kee N, Wilson N, De Vries M, et al. Neogenin and RGMa control neural tube closure and neuroepithelial morphology by regulating cell polarity[J]. J Neurosci,2008,28(48):12643-53.
Keynes R, Krumlauf R. Hox genes and regionalization of the nervous system[J]. Annu Rev Neurosci, 1994,17:109-32.
Komiya Y, Habas R. Wnt signal transduction pathways[J]. Organogenesis,2008,4(2):68-75.
Matsumoto Y, Osumi N. Role of Pax6 in the developing central nervous system[J]. Brain Nerve.2008, 60(4):365-74.
Placzek M, Furley A. Patterning cascades in the neural tube. Neural development[J]. Curr Biol,1996, 6(5):526-29.
Rubenstein JL, Martinez S, Shimamura K, et al. The embryonic vertebrate forebrain:the prosomeric model[J]. Science,1994,266(5185):578-80
Song DL, Chalepakis G, Gruss P, et al. Two Pax-binding sites are required for early embryonic brain expression of an Engrailed-2 transgene[J]. Development,1996,122(2):627-35.
Wilson SI, Edlund T. Neural induction:toward a unifying mechanism[J]. Nat. Neurosci,2001,4: 1161-68.
Wilson SI, Rydstrom A, Trimborn T, et al. The status of Wnt signalling regulates neural and epidermal fates in the chick embryo[J]. Nature,2001,411:325-30.
崔城,宿文辉,于秉治.Cdc25B在小鼠受精卵的表达和定位[J].细胞生物学杂志,2007,29：869-74.
崔城,汤浩,于秉治.Cdc25B蛋白过表达可使小鼠胚胎突破2-细胞期阻滞[J].中国应用生理学杂志,2008,24(1)：99-103.
崔城,于萌,张哲,等.14-3-3蛋白在小鼠受精卵及2-细胞期胚胎中的表达与定位[J].生殖与避孕,2006,26：643.
李志琴,章静波.细胞周期调控与肿瘤(1)[J],癌症进展杂志,2004,2(1)：70-75.
李志琴,章静波.细胞周期调控与肿瘤(2)[J],癌症进展杂志,2004,2(2)：146-50.
申景平,.刘立仁.细胞周期调控机制为癌症研究奠定基础——2001年诺贝尔生理学或医学奖评述[J].国外科技动态.2001：6-9.
张阳,张杰,于爱鸣,等.蛋白激酶A/Cdc25B通路在小鼠卵母细胞G2期阻滞中作用的研究[J].生殖与避孕,2005,25(4)：195-200.
邹向阳,李连宏.细胞周期调控与肿瘤[J].国际遗传学杂志,2006,29(1)：70-73.
Agner J, Alck J, Lukas J, et al. Differential impact of diverse anticancer chemotherapeutics on the Cdc25A-degradation checkpoint pathway[J]. Exp Cell Res,2005,302:162-69.
Aleem E, Kiyokawa H, Kaldis P. Cdc2-Cyclin E complexes regulate the G1/S phase transition[J]. Nat Cell Biol,2005,7:831-36.
Ashcroft NR, Kosinski ME, Wickramasinghe D, et al. The four cdc25 genes from the nematode Caenorhabditis elegans[J]. Gene,1998,214:59-66.
Ashcroft NR, Srayko M, Kosinski ME, et al. RNA-Mediated interference of a cdc25 homolog in Caenorhabditis elegans results in defects in the embryonic cortical membrane, meiosis, and mitosis[J]. Dev Biol,1999,206(1):15-32.
Blomberg I, Hoffmann I. Ectopic expression of Cdc25A accelerates the G(1)/S transition and leads to premature activation of Cyclin E-and Cyclin A-dependent kinases[J]. Mol Cell Biol,1999,19(9): 6183-94.
Bulavin DV, Higashimoto Y, Popoff IJ, et al. Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase[J]. Nature,2001,411:102-07.
Busino L, Donzelli M, Chiesa M, Guardavaccaro D, et al. Degradation of Cdc25A by β-TrCP during S phase and in response to DNA damage [J]. Nature,2003,426:87-91.
Chen MS, Ryan CE, Piwnica-Worms H. Chkl kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding[J]. Mol Cell Biol,2003,23:7488-97.
Damia G, Broggini M. Cell Cycle Checkpoint Proteins and Cellular Response to Treatment by Anticancer Agents[J]. Cell Cycle,2004,3:46-50.
Davezac N, Baldin V, Blot J, et al. Human pEg3 kinase associates with and phosphorylates Cdc25B phosphatase:a potential role for pEg3 in cell cycle regulation[J]. Oncogene,2002,21:7630-41.
Donzelli M, Squatrito M, Ganoth D, et al. Dual mode of degradation of Cdc25A phosphatase[J]. EMBO J,2002,21:4875-84.
Doxsey S, Zimmerman W, Mikule K. Centrosome control of the cell cycle[J]. Trends Cell Biol,2005,15: 303-11.
Draetta G, Eckstein J. Cdc25 protein phosphatases in cell proliferation[J]. Biochim Biophys Acta,1997, 1332(2):M53-M63.
Eckstein JW. Cdc25 as a potential target of anticancer agents[J], Invest New Drugs,2000,18:149-56.
Falck J, Mailand N, Syljuasen RG, et al. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis[J]. Nature,2001,410:842-47.
Fauman EB, Cogswell JP, Lovejoy B, et al. Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A[J]. Cell,1998,93:617-25.
Ferguson AM, White LS, Donovan PJ, et al. Normal cell cycle and checkpoint responses in mice and cells lacking Cdc25B and Cdc25C protein phosphatases [J]. Mol Cell Biol,2005,25 (7):2853-60.
Furnari B, Rhind N, Russell P. Cdc25 mitotic inducer targeted by chkl DNA damage checkpoint kinase[J]. Science,1997,277(5331):1495-97.
Gabrielli BG, De Souza CP, Tonks ID, et al. Cytoplasmic accumulation of Cdc25B phosphatase in mitosis triggers centrosomal microtubule nucleation in HeLa cells [J]. J Cell Sci,1996,109:1081-93.
Graves PR, Lovly CM, Uy GL, et al. Localization of human Cdc25C is regulated both by nuclear export and 14-3-3 protein binding[J]. Oncogene,2001,20,1839-51.
Gruppuso PA, Boylan JM, Vaslet CA. Identification of candidate growth regulating genes that are overexp ressed in late gestation fetal liver in the rat [J]. Biochim Biophy Acta,2000,1494(1):242-47.
Hagopian JC, Kirtley MP, Stevenson LM, et al. Kinetic basis for activation of Cdk2/Cyclin A by phosphorylation[J]. J Biol Chem,2001,276 (1):275-80.
Hoffmann I, Draetta G, Karsenti E. Activation of the phosphatase activity of human cdc25a by a Cdk2-Cyclin E dependent phosphorylation at the G1/S transition[J]. EMBO J,1994,13:4302-10.
Jinno S, Suto K, Nagata A, et al. Cdc25A is a novel phosphatase functioningearly in the cell cycle[J]. EMBOJ,1994,13:1549-56.
Kanemori Y, Uto K, Sagata N. β-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases[J]. Proc Natl Acad Sci USA,2005,102: 6279-84.
Kawabe T. G2 checkpoint abrogators as anticancer drugs[J]. Mol Cancer Ther,2004,3(4):513-19.
Kramer A, Mailand N, Lukas C, et al. Centrosome-ssociated Chkl prevents premature activation of Cyclin-B-Cdkl kinase [J]. Nat Cell Biol,2004,6:884-91.
Kumagai A, Dunphy WG. Binding of 14-3-3 proteins and nuclear export control the intracellular localization of the mitotic inducer Cdc25[J]. Genes Dev,1999,13:1067-72.
Lincoln AJ, Lincoln AJ, Wickramasinghe D, et al. Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation[J]. Nat Genet,2002,30(4):446-9.
Lindqvist A, Kallstrom H, Lundgren A, et al. Cdc25B cooperates with Cdc25A to induce mitosis but has a unique role in activating Cyclin B1-Cdkl at the centrosome [J]. J Cell Biol,2005,171(1):35-45.
Lopez-Girona A, Furnari B, Mondesert O, et al. Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein[J]. Nature,1999,397(6715):172-75,
Mailand N, Podtelejnikov AV, Groth A, et al. Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability [J]. EMBO J,2002,1(21):5911-20.
Manke IA, Nguyen A, Lim D, et al. MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV irradiation[J]. Mol Cell,2005,17: 37-48.
Margolis SS, Perry JA, Weitzel DH, et al. A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25[J]. Mol Biol Cell,2006,17:1779-89.
Matsuoka S, Huang M, Elledge SJ. Linkage of ATM to cell cycle regulation by the Chk2 protein kinase[J]. Science,1998,282:1893-97.
Mikhailov A, Shinohara M, Rieder CL. The p38-mediated stress-activated checkpoint. A rapid response system for delaying progression through antephase and entry into mitosis[J]. Cell Cycle,2005,4: 57-62.
Mirey G, Chartrain I, Froment C, et al. Cdc25B phosphorylated by pEg3 localizes to the centrosome and the spindle poles at mitosis [J]. Cell Cycle,2005,4:806-11.
Miyata H, Doki Y, Shiozaki H, et al. Cdc25B and p53 are independently implicated in radiation sensitivity for human esophageal cancers[J]. Clin Cancer Res,2000,6:4859-65.
Molinari M, Mercurio C, Dominguez J, et al. Human Cdc25A inactivation in response to S phase inhibition and its role in preventing premature mitosis [J]. EMBO Rep,2000,1(1):71-79.
Morgan DO. Rinciples of Cdk regulation[J]. Nature,1995,374 (6518):131-34.
Morris MC, Heitz A, Mery J, et al. An essential phosphorylation-site domain of human Cdc25C interacts with both 14-3-3 and Cyclins [J]. J Biol Chem,2000,275(37):28849-57.
Murray W. Recycling the cell cycle:Cyclins revisited[J]. Cell,2004,116:221-34.
Nilsson I, Hoffmann I. cell cycle regulation by the Cdc25 phosphatase family[J]. Prog Cell Cycle Res, 2000,4:107-14.
Perry JA, Kornbluth S. Cdc25 and Weel:analogous opposites[J]. Cell Div,2007,2(12):1-37.
Reynolds RA, Yem AW, Wolfe CL, et al. Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle[J]. J Mol Biol,1999,293:559-68.
Rudolph J, Epstein DM, Parker L, et al. Specificity of natural and artifical substrates for human Cdc25A[J]. Anal Biochem,2001,289:43-51.
Russell P. Checkpoints on the road to mitosis[J]. TIBS,1998,23:399-402.
Russell P, Nurse P. Cdc25+functions as an inducer in the mitotic control of fission yeast [J]. Cell,1986, 45 (1):145-53.
Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, et al. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints [J]. Annu Rev Biochem,2004,73:39-85.
Sato Y, Sasaki H, Kondo S, et al. Expression of the cdc25B mRNA correlated with that of N-myc in neuroblastoma[J]. Jpn J Clin Oncol,2001,31:428-31.
Sohn J, Rudolph J. Catalytic and chemical compe tence of regulation of Cdc25 phosphatase by oxidation/reduction[J]. Biochemistry,2003,42:10060-70.
Turowski P, Franckhauser C, Morris MC, et al. Functional Cdc25C dual specificity phosphatase is required for S-phase entry in human cells [J]. Mol Biol Cell,2003,14(7):2984-98.
van Vugt MA, Bras A, Medema RH. Restarting the Cell Cycle When the Checkpoint Comes to a Halt[J]. Cancer Res,2005,65(16):7037-40.
Wilker E, Yaffe MB.14-3-3 Proteins-a focus on cancer and human disease[J]. J Mol Cell Cardiol, 2004,37:633-42
Xiao Z, Chen Z, Gunasekera AH, et al. Chkl mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents [J]. J Biol Chem,2003,278(24):21767-73.
Yang J, Winkler K, Yoshida M, et al. Maintenance of G2 arrest in the Xenopus oocyte:a role for 14-3-3-mediated inhibition of Cdc25 nuclear import[J]. EMBO J,1999,18(8):2174-83.
Zeng Y, Forbes KC, Wu Z, et al. Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cdsl or Chkl[J]. Nature,1998,395(6701):507-10.
Zhao H, Watkins JL, Piwnica-Worms H. Disruption of the checkpoint kinase 1/cell division cycle 25A path way abrogates ionizing radiation-induced S and G2 checkpoints[J]. Proc Natl Acad Sci USA, 2002,99:14795-800.
汪锐,程汉华,郭一清,等.脊椎动物Sox基因家族的系统发生分析[J].遗传学报,2002,29(11)：990-94.
Akiyama H, Chaboissier MC, Martin JF, et al. The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6[J]. Genes Dev,2002,16:2813-28.
Ambrosetti DC, Scholer HR, Dailey L, et al. Modulation of The activity of multiple transcriptional activation domains by the DNA binding domains mediates the synergistic action of Sox2 and Oct-3 on the fibroblast growth factor-4 enhancer[J]. J Biol Chem,2000,275:23387-97.
Avilion AA, Nicolis SK, Pevny LH, et al. Multipotent cell lineages in early mouse development depend on Sox2 function[J]. Genes Dev,2003,17(1):126-40.
Botquin V, Hess H, Fuhrmann G, et al. New POU dimmer configuration mediates antagonistic control of anosteopontin preimplantation enhancer by Oct-4 and Sox-2[J]. Genes Dev,1998,12:2073-90.
Bowles J, Schepers G, Koopman P. Phylogeny of the Sox family of developmental transcription factors based on sequence and structural indicators[J]. Dev Biol,2000,227 (2):239-55.
Brazel CY, Limke TL, Osborne JK, et al. Sox2 expression defines a heterogeneous population of neurosphere-forming cells in the adult murine brain[J]. Aging Cell,2005,4(4):197-207.
Collignon J, Sockanathan S, Hacker A, et al. A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2[J]. Development,1996,122:509-20.
Dailey L, Basilico C. Coevolution of HMG domains and homeodomains and the generation of transcriptional regulation by Sox/POU complexes[J]. J Cell Physiol,2001,186:315-28.
Furuta Y, Hogan BLM. BMP4 is essential for lens induction in the mouse embryo[J]. Genes Dev,1998, 12:3764-75.
Gubbay J, Collignon J, Koopman R, et al. A gene mapping to the sex-determining region of the mouse Ychromosome is a member of a novel family of embryonically expressed genes[J]. Nature,1990,346: 245-50.
Harley VR, Lovell-Badge R, Goodfellow P N. Definition of a consensus DNA binding site for Sry[J]. Nucl Acids Res,1994,22:1500-01.
Hawkins JR. Sex determination[J]. Hum Mol Genet,1994,3:1463-67.
Jay P, Sahly I, Goze C, et al. Sox22 is a new member of the Sox gene family, mainly expressed in human nervous tissue[J]. Hum Mol Genet,1997,6:1069-77.
Johnson LR, Lamb KA, Gao QS, et al. Role of the transcription factor Sox-2 in the expression of the FGF-4 gene in embryonal carcinoma cells[J]. Mol Reprod Dev,1998,50:377-86.
Kamachi Y, Uchikawa M, Kondoh H. Pairing Sox off:with partners in the regulation of embryonic development [J]. Trends Genet,2000,16 (4):182-87.
Kanai Y, Kanai-Azuma M, Noce T, et al. Identification of two Sox17 messenger RNA isoforms, with and without the high mobility Group box region, and they are differential expression in mouse Spermatogenesis[J]. The J of Cell Biol,1996(133):667-81.
Koopman P, Munsterberg A, Capel B. Expression of a candidate sex determining gene cloning mouse testis differentiation[J]. Nature,1990,348:140-52.
Miyagi S, Nishimoto M, Saito T, et al. The Sox2 regulatory region 2 functions as a neural s tem cell specific enhancer in the telencephalon[J]. J Biol Chem,2006,281(19):13374-81.
Nishiguchi S, Wood H, Kondoh H, et al. Sox1 directly regulatesthe-crystallin genes and isessential for lens development in mice[J]. Genes Dev,1998,12:776-81.
Nishimoto M, Fukushima A, Okuda A, et al. The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2[J]. Mol Cell Biol,1999,19:5453-65.
Okuda A, Fukushima A, Nishimoto M, et al. UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem cells and extra-embryonic cells[J]. EMBO J,1998,17:2019-32.
Pevny LH, Lovell-Badge R. Sox genes find their feet[J]. Curr Opin Genet Dev,1997,7:338-44.
Pevny L, Placzek M. Sox genes and neural progenitor identity [J]. Curr Opin Neurobiol,2005,15(1): 7-13.
Pontiggia A, Rimini R, Harley BA, et al. Sex-reversing mutations affects the architecture of Sry DNA complexes[J]. EMBO J,1994,13:6115-24.
Russell SR, Sanchez-Soriano N, Wright CR, et al. The Dichaete gene of Drosophila melanogaster encodes a Sox-domain protein required for embryonic segmentation[J]. Development,1996,122: 3669-76.
Scaffidi P, Bianchi ME. Spatially precise DNA bending is an essential activity of the Sox2 transcription factor[J]. J Biol Chem,2001,276:47296-302.
Schepers GE, Teasdale RD, Koopman P. Twenty pairs of Sox:extent, homology, and nomenclature of the mouse and human Sox transcrip tion factor gene families [J]. Dev Cell,2002,3 (2):167-70.
Schilham MW, van Eijk M, van de Wetering M, et al. The murine Sox-4 protein is encoded on a single exon[J]. Nucl Acids Res,1993,21:2009.
Sinclair AH, Berta P, Palmer MS, et al. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif[J]. Nature,1990,346:240-44.
Smith JM, Koopman PA. The ins and outs of transcriptional control:nucleocytoplasmic shuttling in development and disease[J]. Trends Genet,2004,20:4-8.
Taranova OV, Magness ST, Fagan BM, et al. Sox2 is a dose-dependent regulator of retinal neural progenitor competence[J]. Genes & Dev,2006,20:1187-202.
Tokuzawa Y, Kaiho E, Maruyama M, et al. Fbx15 is a novel target of Oct3/4 but is dispensable for embryonic stem cell self-renewal and mouse development[J]. Mol Cell Biol,2003,23:2699-708.
van de Wetering M, Oosterwegel M, van Norren K, et al. Sox24, an Sry-like HMG box protein is a transcriptionnal activator in lymphocytes[J]. EMBO J,1993,12:3847-54.
Wegner M. From head to toes:the multiple facets of Sox proteins[J]. Nucl Acids Res,1999,27: 1409-20.
Wiebe M S, Wilder P J, Kelly D, et al. Isolation, characterization, and differential expression of the murine Sox-2 promoter[J]. Gene,2000,246:383-93.
Wilson M, Koopman P. Matching Sox:Partner proteins and co-factors of the Sox family of transcriptional regulators [J]. Curr Opi n Genet Dev,2002,12 (4):441-46.
Wood H B, Episkopou V. Comparative expression of the mouse Soxl, Sox2 and Sox3 genes from pre-gastrulation to early somites[J]. Mech Dev,1999,86:197-201.
Wotton D, Lake RA, Farr CG, et al. The high mobility group transcription factor, Sox4, transactivates the human CD2 enhancer[J]. J Biol Chem,1995,270:7515-22.
Wright E, Hargrave MR, Christiansen J, et al. The Sry-related gene Sox9 is expressed during chondrogenesis in mouse embryos[J]. Nature Genet,1995,9:15-20.
Yuan HB, Corbi N, Basilico C, et al. Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3[J]. Genes Dev,1995,9:2635-45.
Zhou R, Guo Y, Cheng H, et al. Comparative tree of sex-determining region Y (Sry) and Sry box genes[J]. Acta Zoologica Sinica,1997,43(2):192-96.
Adayev T, Chen-Hwang MC, Murakami N, et al. Mnb/Dyrk1A phosphorylation regulates the interactions of synaptojanin 1 with endocytic accessory proteins [J]. Biochem Biophys Res Commun, 2006,351:1060-65.
Bahler J, Pringle JR. Pomlp, a fission yeast protein kinase that provides positional information for both polarized growth and cytokinesis[J]. Genes,1998,12:1356-70.
Becker W, Joost HG. Structural and functional characteristics of Dyrk, a novel subfamily of protein kinases with dual specificity [J]. Prog Nucleic Acid Res Mol Biol,1999,62:1-17.
Campbell LE, Proud CG. Differing substrate specificities of members of the Dyrk family of arginine-directed protein kinases[J]. FEBS Lett,2002,510:31-36.
de Graaf K, Czajkowska H, Rottmann S, et al. The protein kinase Dyrk1A phosphorylates the splicing factor SF3b1/SAP155 at Thr434, a novel in vivo phosphorylation site[J]. BMC Biochem,2006,7:7.
de Graaf K, Hekerman P, Spelten O, et al. Characterization of Cyclin L2, a Novel Cyclin with an Arginine/Serine-rich Domain[J]. J Biol Chem.2004,6,279(6):4612-24.
Deng X, Ewton DZ, Mercer SE, et al. Mirk/dyrklB decreases the nuclear accumulation of class Ⅱ histone deacetylases during skeletal muscle differentiation[J]. J Biol Chem,2005,280:4894-905.
Deng X, Mercer SE, Shah S, et al. The cyclin-dependent kinase inhibitor p27Kip1 is stabilized in G(0) by Mirk/dyrklB kinase[J]. J Biol Chem,2004,279:22498-504.
Fischbach KF, Technau G. Cell degeneration in the developing optic lobes of the sine oculis and small-optic-lobes mutants of Drosophila melanogaster[J]. Dev Biol,1984,104:219-39.
Fotaki V, Dierssen M, Alcantara S, et al. Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice[J]. Mol Cell Biol,2002,22(18): 6636-47.
Garrett S, Broach J. Loss of Ras activity in Saccharomyces cerevisiae is suppressed by disruptions of a new kinase gene, YAKI, whose product may act downstream of the cAMP-dependent protein kinase[J]. Genes Dev,1989,31336-48.
Garrett S, Menold MM, Broach JR. The Saccharomyces cerevisiae YAK1 gene encodes a protein kinase that is induced by arrest early in the cell cycle[J]. Mol Cell Biol,1991,11:4045-52.
Geiger JN, Knudsen GT, Panek L, et al. mDYRK3 kinase is expressed selectively in late erythroid progenitor cells and attenuates colony-forming unit-erythroid development[J]. Blood,2001, 97(4):901-10.
Guimera J, Casas C, Estivill X, et al. Human minibrain homologue (MNBH/DYRK1):characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome[J]. Genomics,1999,57(3):407-18.
Guimera J, Casas C, Pucharcos C, et al. A human homologue of Drosophila minibrain (Mnb) is. expressed in the neuronal regions affected in Down syndrome and maps to the critical region[J]. Hum Mol Genet,1996,9:1305-10.
Hammerle B, Carnicero A, Elizalde C, et al. Expression patterns and subcellular localization of the Down syndrome candidate protein Mnb/Dyrk1A suggest a role in late neuronal differentiation[J]. Eur J Neurosci,2003a,17:2277-86.
Hammerle B, Vera-Samper E, Speicher S, et al. Mnb/DyrklA is transiently expressed and asymmetrically segregated in neural progenitor cells at the transition to neurogenic divisions[J]. Dev Biol,2002,246:259-73.
Himpel S, Panzer P, Eirmbter K, et al. Identification of the autophosphorylation sites and characterization of their effects in the protein kinase DYRK1A[J]. Biochem J,2001,359:497-505.
Himpel S, Tegge W, Frank R, et al. Specificity determinants of substrate recognition by the protein kinase Dyrk1A[J]. J Biol Chem,2000,275:2431-38.
Kasper M, Regl G, Frischauf AM, et al. GLI transcription factors:mediators of oncogenic Hedgehog signalling[J]. Eur J Cancer,2006,42(4):437-45.
Kelly PA, Rahmani Z. Dyrk1A Enhances the Mitogen-activated Protein Kinase Cascade in PC 12 Cells by Forming a Complex with Ras, B-Raf, and MEK1[J]. Mol Biol Cell,2005,16:3562-73.
Kentrup H, Becker W, Heukelbach J, et al. Dyrk, a dual specificity protein kinase with unique structural features whose activity is dependent on tyrosine residues between subdomains Ⅶ and Ⅷ[J]. J Biol Chem,1996,271:3488-95.
Kim D, Won J, Shin DW, et al. Regulation of Dyrk1A kinase activity by 14-3-3[J]. Biochem Biophys Res Commun,2004,323:499-504.
Lee K, Deng X, Friedman E. Mirk protein kinase is a mitogen-activated protein kinase substrate that mediates survival of colon cancer cells[J]. Cancer Res,2000,60:3631-37.
Lee SY, Wenk MR, Kim Y, et al. Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses[J]. Proc Natl Acad Sci USA,2004,101:546-51.
Lochhead PA, Sibbet G, Morrice N, et al. Activation-Loop Autophosphorylation Is Mediated by a Novel Transitional Intermediate Form of Dyrks[J]. Cell,2005,121:925-36.
Mao J, Maye P, Kogerman P, et al. Regulation of Glil Transcriptional Activity in the Nucleus by Dyrk1[J]. J Biol Chem,2002,277(38):35156-61.
Mercer SE, Ewton DZ, Deng X, et al. Mirk/Dyrk1B mediates survival during the differentiation of C2C12 myoblasts[J]. J Biol Chem,2005,280:25788-801.
Marti E, Altafaj X, Dierssen M, et al. Dyrk1A expression pattern supports specific roles of this kinase in the adult central nervous system[J]. Brain Res,2003,964:250-63.
Miyata Y, Nishida E. Distantly related cousins of MAP kinase:biochemical properties and possible physiological functions[J]. Biochem Biophys Res Commun,1999,266:291-95.
Nigg EA. Cyclin-dependent protein kinases:key regulators of the eukaryotic cell cycle[J]. Bioessays, 1995,17:471-80.
Okui M, Ide T, Morita K, et al. High-level expression of the Mnb/Dyrk1 A gene in brain and heart during rat early development[J]. Genomics,1999,62:165-71.
Pang KM, Ishidate T, Nakamura K, et al. The minibrain kinase homolog, mbk-2, is required for spindle positioning and asymmetric cell division in early C. elegans embryos[J]. Dev Biol,2004,265: 127-39.
Papin C, Denouel A, Calothy G, et al. Identification of signalling proteins interacting with B-Raf in the yeast two-hybrid system[J]. Oncogene,1996,12:2213-21.
Rahmani Z, Lopes C, Rachidi M, et al. Expression of the Mnb (dyrk) Protein in Adult and Embryonic Mouse Tissues[J]. Biochem Biophys Res Commun,1998,253(2):514-8.
Shindoh N, Kudoh J, Maeda H, et al. Cloning of a human homolog of the Drosophila minibrain/rat Dyrk gene from "the Down syndrome critical region" of chromosome 21 [J]. Biochem Biophys Res Commun,1996,225:92-99.
Song WJ, Chung SH, Kurnit DM. The murine Dyrk protein maps to chromosome 16, localizes to the nucleus, and can form multimers[J]. Biochem Biophys Res Commun,1997,231:640-44.
Souza GM, Lu S, Kuspa A. YakA, a protein kinase required for the transition from growth to development in Dictyostelium[J]. Development,1998,125:2291-302.
Tejedor F, Zhu XR, Kaltenbach E, et al. Minibrain:a new protein kinase family involved in postembryonic neurogenesis in Drosophila[J]. Cell,1995,14:287-301.
van Es S, Weening KE, Devreotes PN. The protein kinase YakA regulates G-protein-linked signaling responses during growth and development of Dictyostelium[J]. J Biol Chem,2001,276,30761-65.
Wegiel J, Kuchna I, Nowicki K, et al. Cell type-and brain structure-specific patterns of distribution of minibrain kinase in human brain[J]. Brain Res,2004,1010:69-80.
Widmann C, Gibson S, Jarpe MB, et al. Mitogen-activated protein kinase:conservation of a three-kinase module from yeast to human[J]. Physiol Rev,1999,79:143-80.
Yang EJ, Ahn YS, Chung KC. Protein kinase Dyrk1 activates cAMP response element-binding protein during neuronal differentiation in hippocampal progenitor cells[J]. J Biol Chem,2001,276:39819-24.
Zou Y, Ewton DZ, Deng X, et al. Mirk/dyrk1B kinase destabilizes cyclin D1 by phosphorylation at threonine 288[J]. J Biol Chem,2004,279:27790-98.
刘玉如,佘锐萍,靳红等.P物质及其mRNA在家兔圆小囊组织内表达的研究[J].科学技术与工程,2005,5(3)：147-51.
武胜昔,吕葆真,李继硕.α-和β-CGRP及PPTAmPNAs在大鼠三叉神经节神经元中的共同表达[J].中国神经科学杂志,1997,4(1)：1-6.
王廷华,冯忠堂.分子杂交理论与技术[M].北京：科学出版社,2005,7-8.
张魁华,舒斯云,包新民.大鼠纹状体边缘区P物质受体的原位杂交和免疫组织化学研究[J].神经解剖学杂志,2000,16(4)：359-62.
张维铭.现代分子生物学实验手册[M].北京：科学出版社,2003,311-17.
Harrison MB, Kumar S, Hubbard CA, et al. Early changes in neuropeptide mRNA expression in the striatum following reserpine treatment[J]. Exp Neurol,2001,167:321-28.
Shigeyoshi Y, Maebayashi Y, Okamura H. Co-localization of preprosomatostatin mRNA and preprotachykinin A mRNA in neurons of the rat suprachiasmatic nucleus[J]. Brain Res Mol Brain Res, 1997,48:159-63.
Szallasi A, Farkas-Szallasi T, Tucker Ject. Effects of systemic resiniferatoxin treatment on substance P mRNA in rat dorsal root ganglia and substance P receptor mRNA in the spinal dorsal horn[J]. Brain Res,1999,815:177-84.
蔡文琴.发育神经生物学[M].北京：科学出版社,2007,93-144.
丁斐.神经生物学[M].北京：科学出版社,2007,25-88.
D.L.斯佩克特等著；黄培堂等译.细胞试验指南(下册)[M].北京：科学出版社,2001,1129-37.
Benazeraf B, Chen Q, Peco E, et al. Identification of an unexpected link between the Shh pathway and a G2/M regulator, the phosphatase CDC25B [J]. Devel Biol,2006,294:133-47.
Jinno S, Suto K, Nagata A, et al. Cdc25A is a novel phosphatase functioning early in the cell cycle[J]. EMBOJ,1994,13,1549-56.
Hamburger V, Hamilton HL. A series of normal s in the development of the chick embryo[J]. J Morphol, 1951,88:49-92.
Hoffmann I, Draetta G, Karsenti E. Activation of the phosphatase activity of human Cdc25A by a Cdk2-cyclin E dependent phosphorylation at the G1/S transition[J]. EMBO J,1994,13:4302-10.
Kakizuka A, Sebastian B, Borgmeyer U, et al. A mouse cdc25 homolog is differentially and developmentally expressed[J]. Genes Dev,1992,6(4):578-90.
Kumagai A, Dunphy WG. Regulation of the cdc25 protein during the cell cycle in Xenopus extracts[J]. Cell,1992,70:139-51.
Lindqvist A, Kallstrom H, Lundgren A, et al. Cdc25B cooperates with Cdc25A to induce mitosis but has a unique role in activating cyclin B1-Cdkl at the centrosome[J]. J Cell Biol,2005,171:35-45.
Mailand N, Podtelejnikov AV, Groth A, et al. Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability[J]. EMBO J,2002,21(21):5911-20.
Mizoguchi S, Kim KH. Expression of cdc25 Phosphatases in the Germ Cells of the Rat Testis[J]. Biol Reprod,1997,56(6):1474-81.
Molinari M, Mercurio C, Dominguez J, et al. Human Cdc25A inactivation in response to S phase inhibition and its role in preventing premature mitosis[J]. EMBO Rep,2000,1:71-79.
Okazaki K, Hayashida K, Iwashita J, et al. Isolation of a cDNA encoding the Xenopus homologue of mammalian Cdc25A that can induce meiotic maturation of oocytes[J]. Gene,1996,178:111-14.
Ogg S, Gabrielli B, Piwnica-Worms H. Purification of a serine kinase that associates with and phosphorylates human cdc25c on serine 216[J]. J Biol Chem,1994,269:30461-69.
Perry JA, Kornbluth S. Cdc25 and Weel:analogous opposites[J]. Cell Div,2007,2:1-40.
Ravnik SE, Wolgemuth DJ. The developmentally restricted pattern of expression in the male germ line of a murine cyclin A, cyclin A2, suggests roles in both mitotic and meiotic cell cycles[J]. Dev Biol, 1996,173:69-78.
Rhee K, Wolgemuth D. Cdk family genes are expressed not only in dividing but also in terminally differentiated mouse germ cells, suggesting their possible function during both cell division and differentiation[J]. Dev Dynam,1995,204:406-20.
Solc P, Saskova A, Baran V, et al. CDC25A phosphatase controls meiosis I progression in mouse oocytes[J]. Dev Biol,2008,317(1):260-9.
Sweeny C, Martin M, Kubelka M, et al. A distinct cyclin A is expressed in the germ cells in the mouse[J]. Development,1996,122:53-64.
Wickramasinghe D, Becker S, Ernst MK, et al. Two CDC25 homologues are differentially expressed during mouse Development[J]. Development,1995,121:2047-56.
Alphey L, Jimenez J, White-Cooper H, et al. Twine, a cdc25 homolog that functions in the male and female germline of Drosophila[J]. Cell,1992,69:977-88.
Barre B, Vigneron A, Coqueret O. The STAT3 transcription factor is a target for the Myc and riboblastoma proteins on the Cdc25A promoter[J]. J Biol Chem,2005,280:15673-81.
Benazeraf B, Chen Q, Peco E, et al. Identification of an unexpected link between the Shh pathway and a G2/M regulator, the phosphatase CDC25B[J]. Devel Biol,2006,294:133-47.
Boutros R, Ducommun B. Asymmetric localization of the CDC25B phosphatase to the mother centrosome during interphase[J]. Cell Cycle,2008,7:401-06.
Boutros R, Dozier C, Ducommun B. The when and wheres of Cdc25 phosphatases[J]. Curr Opin Cell Biol,2006,18:185-91.
Briscoe J, Ericson J. Specification of neuronal fates in the ventral neural tube[J]. Curr Opin Neurobiol, 2001,11(1):43-9.
Draetta G, Eckstein J. Cdc25 protein phosphatases in cell proliferation[J]. Biochim Biophys Acta,1997, 1332:M53-63.
Edgar B. Diversification of cell cycle controls in developing embryos[J]. Curr Opin Cell Biol,1995,7: 815-24.
Edgar BA, O'Farrell PH. Genetic control of cell division patterns in the Drosophila embryo[J]. Cell, 1989,57:177-87
Edgar BA, O'Farrell PH. The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string[J]. Cell,1990,62:469-80.
Ericson J, Rashbass P, Schedl A, et al. Pax6 controls progenitor cell identity and neuronal fate in response to gradedShh signaling. Cell,1997,90:169-80.
Gasparotto D, Maestro R, Piccinin S, et al. Overexpression of CDC25A and CDC25B in head and neck cancers[J]. Cancer Res,1997,57:2366-68.
Hamburger V, Hamilton HL. A series of normal s in the development of the chicken embryo [J]. Dev Dyn,1992,195(4):231-72.
Kakizuka A, Sebastian B, Borgmeyer U, Hermans-Borgmeyer I, et al. A mouse cdc25 homolog is differentially and developmentally expressed[J] Genes Dev,1992,6:578-90.
Kumagai A, Dunphy WG. The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system[J]. Cell,1991,64:903-14.
Levin M, Johnson RL, Stern CD, et al. A molecular pathway determining left-right asymmetry in chick embryogenesis[J]. Cell,1995,82:803-14.
Lewin B. Driving the cell cycle:M-phase kinase, its partners, and substrates [J]. Cell,1990,61:743-52.
Mac AA, Werb Z, Mirkes PE. Characterization of the unusually rapid cell cycles during rat gastrulation[J]. Development,1993,117:873-83.
Mailand N, Podtelejnikov AV, Groth A, et al. Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability[J]. EMBO J,2002,21:5911-20.
Nagata A, Igarashi M, Jinno S, et al. An additional homolog of the fission yeast cdc25+gene occurs in humans and is highly expressed in some cancer cells[J]. New Biol,1991,3:959-68.
Nilsson I, Hoffmann I. Cell cycle regulation by the Cdc25 phosphatase family [J]. Prog Cell Cycle Res, 2000,4:107-14.
Nurse P. Universal control mechanism regulating onset of M-phase[J]. Nature,1990,344:503-08.
Perry JA, Kornbluth S. Cdc25 and Weel:analogous opposites[J]. Cell Div,2007,2:1-40.
Raya A, Izpisua Belmonte JC. Unveiling the establishment of left-right asymmetry in the chick embryo[J]. Mech Devel,2004,121:1043-54.
Rex M, Orme A, Uwanogho D, et al. Dynamic expression of chicken Sox2 and Sox3 genes in ectoderm induced to form neural tissue[J]. Devel Dyna,1997,209:323-32.
Rowitch DH, S-Jacques B, Lee SM, et al. Sonic hedgehog regulates proliferation and inhibits differentiation of CNS precursor cells[J]. J Neurosci,1999,19(20):8954-65.
Russell P, Nurse P. cdc25+functions as an inducer in the mitotic control of fission[J]. Cell,1986,45: 145-53.
Toogood PL. Progress toward the development of agents to modulate the cell cycle[J]. Curr Opin Chem Biol,2002,6:472-78.
Varmeh-Ziaie S, Manfredi JJ. The dual specificity phosphatase Cdc25B, but not the closely related Cdc25C, is capable of inhibiting cellular proliferation in a manner dependent upon its catalytic activity[J]. J Biol Chem,2007,282:24633-41.
Wechsler-Reya RJ, Scott MP. Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog[J]. Neuron,1999,22(1):103-14.
Barre B, Vigneron A, Coqueret O. The STAT3 transcription factor is a target for the Myc and riboblastoma proteins on the Cdc25A promoter[J]. J Biol Chem,2005,280:15673-81.
Boutros R, Lobjois V, Ducommun B. Cdc25 phosphatases in cancer cells:key players? Good targets? [J]. Nat Rev Cancer,2007,7(7):495-507.
Bylund M, Andersson E, Novitch BG, et al. Vertebrate neurogenesis is counteracted by Soxl-3 activity[J]. Nat Neurosci,2003,6:1162-68.
Ellis P, Fagan BM, Magness ST, et al. Sox2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult[J]. Dev Neurosci,2004,26(2-4):148-65.
Episkopou V. Sox2 functions in adult neural stem cells[J]. Trends Neurosci,2005,28:219-21.
Foshay KM, Gallicano GI. Regulation of Sox2 by STAT3 initiates commitment to the neural precursor cell fate[J]. Stem Cells Dev,2008,17:269-78.
Graham V, Khudyakov J, Ellis P, et al. Sox2 functions to maintain neural progenitor identity[J]. Neuron, 2003,39:749-65.
Jinno S, Suto K, Nagata A, et al. Cdc25A is a novel phosphatase functioning early in the cell cycle[J]. EMBOJ,1994,13:1549-56.
Kishi M, Mizuseki K, Sasai N, et al. Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm[J]. Development,2000,127(4):791-800.
Kumagai A, Dunphy WG. The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system[J]. Cell,1991,64:903-14.
Li M, Pevny L, Lovell-Badge R, et al. Generation of purified neural precursors from embryonic stem cells by lineage selection[J]. Curr Biol,1998,8(17):971-74.
Mailand N, Podtelejnikov AV, Groth A, et al. Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability[J]. EMBO J,2002,21:5911-20.
Molinari M, Mercurio C, Dominguez J, et al. Human Cdc25 A inactivation in response to S phase inhibition and its role in preventing premature mitosis[J]. EMBO Rep,2000,1:71-79.
Papanayotou C, Mey A, Birot AM, et al. A mechanism regulating the onset of Sox2 expression in the embryonic neural plate[J]. PLoS Biol,2008,6(1):0109-23.
Rex M, Orme A, Uwanogho D, et al. Dynamic expression of chicken Sox2 and Sox3 genes in ectoderm induced to form neural tissue[J]. Devel Dyna,1997,209:323-32.
Taranova OV, Magness ST, Fagan BM, et al. Sox2 is a dose-dependent regulator of retinal neural progenitor competence[J]. Genes & Dev.2006,20:1187-202.
Uwanogho D, Rex M, Cartwright EJ, et al. Embryonic expression of the chicken Sox2, Sox3 and Sox11 suggests an interactive role in neuronal development[J]. Mech Dev,1995,49:23-36.
Zappone MV, Galli R, Catena R, et al. Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells[J]. Development,2000,127(11):2367-82.
Adayev T, Chen-Hwang MC, Murakami N, et al. MNB/DYRK1A phosphorylation regulates the interactions of synaptojanin 1 with endocytic accessory proteins[J]. Biochem Biophys Res Commun, 2006,351:1060-65.
Alexiades MR, Cepko CL. Subsets of retinal progenitors display temporally regulated and distinct biases in the fates of their progeny[J]. Development,1997,124:1119-31.
Bahler J, Pringle JR. Pomlp, a fission yeast protein kinase that provides positional information for both polarized growth and cytokinesis[J]. Genes,1998,12:1356-70.
Boutros R, Dozier C, Ducommun B. The when and wheres of Cdc25 phosphatases[J]. Curr Opin Cell Biol,2006,18:185-91.
Boutros R, Lobjois V, Ducommun B. Cdc25 phosphatases in cancer cells:key players? Good targets? [J]. Nature,2007,7:495-507.
Collignon J, Sockanathan S, Hacker A, et al. A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2[J]. Development,1996,122:509-20.
de Graaf K, Hekerman P, Spelten O, et al. Characterization of Cyclin L2, a Novel Cyclin with an Arginine/Serine-rich Domain[J]. J Biol Chem,2004,6,279(6):4612-24.
Episkopou, V. Sox2 functions in adult neural stem cells[J]. Trends Neurosci,2005,28:219-21.
Es SV, Weening KE, Devreotes PN. The protein kinase YakA regulates G-protein-linked signaling responses during growth and development of Dictyostelium[J]. J Biol Chem,2001,276:30761-65.
Garrett S, Broach J. Loss of Ras activity in Saccharomyces cerevisiae is suppressed by disruptions of a new kinase gene, YAKI, whose product may act downstream of the cAMP-dependent protein kinase[J]. Genes Dev,1989,31336-48.
Garrett S, Menold MM, Broach JR. The Saccharomyces cerevisiae YAK1 gene encodes a protein kinase that is induced by arrest early in the cell cycle[J]. Mol Cell Biol,1991,11:4045-52.
Hammerle B, Vera-Samper E, Speicher S, et al. Mnb/Dyrk1A is transiently expressed and asymmetrically segregated in neural progenitor cells at the transition to neurogenic divisions[J]. Dev Biol,2002,246:259-73.
Hermeking H, Benzinger A.14-3-3 proteins in cell cycle regulation[J]. Semin Cancer Biol,2006,16: 183-92.
Huttner WB, Brand M. Asymmetric division and polarity of neuroepithelial cells[J]. Curr Opin Neurobiol,1997,7:29-39.
Kelly PA, Rahmani Z. Dyrk1A Enhances the Mitogen-activated Protein Kinase Cascade in PC 12 Cells by Forming a Complex with Ras, B-Raf, and MEK1[J]. Mol Biol Cell,2005,16:3562-73.
Kentrup H, Becker W, Heukelbach J, et al. Dyrk, a dual specificity protein kinase with unique structural features whose activity is dependent on tyrosine residues between subdomains Ⅶ and Ⅷ[J]. J Biol Chem,1996,271:3488-95.
Kim D, Won J, Shin DW, et al. Regulation of Dyrk1A kinase activity by 14-3-3[J]. Biochem Biophys Res Commun,2004,323:499-504.
Lochhead PA, Sibbet G, Morrice N, et al. Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of Dyrks[J]. Cell,2005,121:925-36.
Miyata Y, Nishida E. Distantly related cousins of MAP kinase:biochemical properties and possible physiological functions[J]. Biochem Biophys Res Commun,1999,266:291-95.
Nigg EA. Cyclin-dependent protein kinases:key regulators of the eukaryotic cell cycle[J]. Bioessays, 1995,17:471-80
Papin C, Denouel A, Calothy G, et al. Identification of signalling proteins interacting with B-Raf in the yeast two-hybrid system [J]. Oncogene,1996,12:2213-21.
Perry JA, Kornbluth S. Cdc25 and Weel:analogous opposites[J]. Cell Div,2007,2:1-40.
Rex M, Orme A, Uwanogho D, et al. Dynamic expression of chicken Sox2 and Sox3 genes in ectoderm induced to form neural tissue[J]. Devel Dyna,1997,209:323-32.
Rudolph J. Cdc25 Phosphatases:Structure, Specificity, and Mechanism[J]. Biochemistry,2007,46: 3595-604.
Souza GM, Lu S, Kuspa A. YakA, a protein kinase required for the transition from growth to development in Dictyostelium[J]. Development,1998,125:2291-302.
Takahashi T, Goto T, Miyama S, et al. Sequence of neuron origin and neocortical laminar fate:Relation to cell cycle of origin in the developing murine cerebral wall[J]. J Neurosci,1999,19:10357-71.
Tejedor F, Zhu XR, Kaltenbach E, et al. Minibrain:a new protein kinase family involved in postembryonic neurogenesis in Drosophila[J]. Cell,1995,14:287-301.
Temple S, Qian X. Vertebrate neural progenitor cells:subtypes and regulation[J]. Curr Opin Neurobiol, 1996,6:11-17.
Wegiel J, Kuchna I, Nowicki K, et al. Cell type-and brain structure-specific patterns of distribution of minibrain kinase in human brain[J]. Brain Res,2004,1010:69-80.
Wen Z, Darnell JE Jr. Mapping of Stat3 serine phosphorylation to a single residue(727) and evidence that serine phosphorylation has no influence on DNA binding of Statl and Stat3[J]. Nucleic Acids Res, 1997,25:2062-67.
Wen Z, Zhong Z, Darnell JE Jr. Maximal activation of transcription by Statl and Stat3 requires both tyrosine and serine phosphorylation[J]. Cell,1995,82:241-50.
Yang EJ, Ahn YS, Chung KC. Protein kinase Dyrkl activates cAMP response element-binding protein during neuronal differentiation in hippocampal progenitor cells[J]. J Biol Chem,2001,276:39819-24.