Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb
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- 作者：Diego García-González ; Verónica Murcia-Belmonte…
- 关键词：Neural stem cell ; Interneuron ; Cell migration ; FGF2 ; Primary cilium ; GnRH neuron ; Kallmann syndrome
- 刊名：Brain Structure and Function
- 出版年：2016
- 出版时间：January 2016
- 年：2016
- 卷：221
- 期：1
- 页码：239-260
- 全文大小：4,743 KB
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Verónica Murcia-Belmonte (1) (8)
Pedro F. Esteban (1)
Felipe Ortega (2)
David Díaz (3)
Irene Sánchez-Vera (4) (7)
Rafael Lebrón-Galán (1)
Laura Escobar-Castañondo (5)
Luis Martínez-Millán (5)
Eduardo Weruaga (3)
José Manuel García-Verdugo (4)
Benedikt Berninger (2)
Fernando de Castro (1)
1. Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Toledo, Spain
6. Clinical Neurobiology, German Center for Cancer Research (DKFZ), Heidelberg, Germany
8. Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain
2. University Medical Center Johannes Gutenberg, University of Mainz, Mainz, Germany
3. Instituto de Neurociencias de Castilla y León-INCyL, Universidad de Salamanca, Salamanca, Spain
4. Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, Valencia, Spain
7. Unidad mixta de Esclerosis múltiple y neurorregeneración, IIS Hospital La Fe, Valencia, Spain
5. Departmento de Neurosciencias, Facultad de Medicina, Universidad del País Vasco, Leioa, Spain - 刊物主题：Neurosciences; Cell Biology; Neurology;
- 出版者：Springer Berlin Heidelberg
- ISSN：1863-2661
文摘
New subventricular zone (SVZ)-derived neuroblasts that migrate via the rostral migratory stream are continuously added to the olfactory bulb (OB) of the adult rodent brain. Anosmin-1 (A1) is an extracellular matrix protein that binds to FGF receptor 1 (FGFR1) to exert its biological effects. When mutated as in Kallmann syndrome patients, A1 is associated with severe OB morphogenesis defects leading to anosmia and hypogonadotropic hypogonadism. Here, we show that A1 over-expression in adult mice strongly increases proliferation in the SVZ, mainly with symmetrical divisions, and produces substantial morphological changes in the normal SVZ architecture, where we also report the presence of FGFR1 in almost all SVZ cells. Interestingly, for the first time we show FGFR1 expression in the basal body of primary cilia in neural progenitor cells. Additionally, we have found that A1 over-expression also enhances neuroblast motility, mainly through FGFR1 activity. Together, these changes lead to a selective increase in several GABAergic interneuron populations in different OB layers. These specific alterations in the OB would be sufficient to disrupt the normal processing of sensory information and consequently alter olfactory memory. In summary, this work shows that FGFR1-mediated A1 activity plays a crucial role in the continuous remodelling of the adult OB Keywords Neural stem cell Interneuron Cell migration FGF2 Primary cilium GnRH neuron Kallmann syndrome