A complex RARE is required for the majority of Nedd9 embryonic expression

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• 作者：Danielle C. Knutson ; Margaret Clagett-Dame
• 关键词：All ; trans retinoic acid (atRA) ; Retinoic acid response element (RARE) ; Nedd9 ; Hef1 ; Nervous system development ; Cranial nerves
• 刊名：Transgenic Research
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：24
• 期：1
• 页码：123-134
• 全文大小：2,566 KB
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• 作者单位：Danielle C. Knutson (1)
  Margaret Clagett-Dame (1)
  
  1. Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, 53706, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Molecular Medicine
  Plant Genetics and Genomics
  Animal Genetics and Genomics
  Plant Sciences
  Human Genetics
  
• 出版者：Springer Netherlands
• ISSN：1573-9368

文摘

Neural precursor cell expressed, developmentally down-regulated 9 (Nedd9, Casl, Hef1, p105cas, Ef1) is a scaffolding protein that assembles complexes involved in regulating cell adhesion, migration, division, and survival. Nedd9 is found very early in the developing embryonic nervous system. A highly conserved complex retinoic acid response element (RARE) is located 485 base pairs (bp) upstream of exon 2B in the promoter of the Nedd9 gene. Mice transgenic for a 5.2 kilobase (kb) region of the 2B Nedd9 promoter containing the RARE upstream of a lacZ reporter gene [Nedd9(RARE)-lacZ] show a large subset of the normal endogenous Nedd9 expression including that in the caudal hindbrain neuroepithelium, spinal cord, dorsal root ganglia (drg) and migrating neural crest (ncc). However, the transgenic mice do not recapitulate the native Nedd9 expression pattern in presumptive rhombomeres (pr) 3 and 5 of the early hindbrain, the base of the neuroepithelium in the midbrain, nor the forebrain telencephalon. Thus, the 5.2?kb region containing the intact RARE drives a large subset of Nedd9 expression, with additional sequences outside of this region needed to define the full complement of expression. When the 5.2?kb construct is modified (eight point mutations) to eliminate responsiveness of the RARE to all-trans retinoic acid (atRA) [Nedd9(mutRARE)-lacZ], virtually all β-galactosidase (β-gal, lacZ) expression is lost. Exposure of Nedd9(RARE)-lacZ transgenic embryos to excess atRA at embryonic day 8.0 (E8.0) leads to rostral ectopic transgene expression within 6?h whereas the Nedd9(mutRARE)-lacZ mutant does not show this effect. Thus the RARE upstream of the Nedd9 2B promoter is necessary for much of the endogenous gene expression during early development as well as ectopic expression in response to atRA.