Fibroblast growth factor 10 is a negative regulator of postnatal neurogenesis in the mouse hypothalamus

被引:19
|
作者
Goodman, Timothy [1 ]
Nayar, Stuart G. [1 ]
Clare, Shaun [1 ]
Mikolajczak, Marta [1 ]
Rice, Ritva [2 ]
Mansour, Suzanne [3 ]
Bellusci, Saverio [4 ,5 ]
Hajihosseini, Mohammad K. [1 ]
机构
[1] Univ East Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England
[2] Univ Helsinki, Inst Biotechnol, Viikinkaari 9, Helsinki 00014, Finland
[3] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA
[4] Univ Calif Los Angeles, Saban Res Inst Childrens Hosp Angeles, Pediat, Los Angeles, CA 90027 USA
[5] Univ Justus Liebig, Excellence Cluster Cardio Pulm Syst, D-35392 Giessen, Germany
来源
DEVELOPMENT | 2020年 / 147卷 / 13期
基金
英国生物技术与生命科学研究理事会;
关键词
Postnatal neurogenesis; Fibroblast growth factors; Tanycytes; Cell movement; Lineage tracing; Hypothalamus; Mouse; NEURAL STEM-CELLS; ADULT NEUROGENESIS; TANYCYTES; BRAIN; NEURONS; FGF10; POPULATIONS; GENES;
D O I
10.1242/dev.180950
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
New neurons are generated in the postnatal rodent hypothalamus, with a subset of tanycytes in the third ventricular (3V) wall serving as neural stem/progenitor cells. However, the precise stem cell niche organization, the intermediate steps and the endogenous regulators of postnatal hypothalamic neurogenesis remain elusive. Quantitative lineage-tracing in vivo revealed that conditional deletion of fibroblast growth factor 10 (Fgf10) from Fgf10-expressing beta-tanycytes at postnatal days (P)4-5 results in the generation of significantly more parenchymal cells by P28, composed mostly of ventromedial and dorsomedial neurons and some glial cells, which persist into adulthood. A closer scrutiny in vivo and ex vivo revealed that the 3V wall is not static and is amenable to cell movements. Furthermore, normally beta-tanycytes give rise to parenchymal cells via an intermediate population of alpha-tanycytes with transient amplifying cell characteristics. Loss of Fgf10 temporarily attenuates the amplification of beta-tanycytes but also appears to delay the exit of their alpha-tanycyte descendants from the germinal 3V wall. Our findings suggest that transience of cells through the alpha-tanycyte domain is a key feature, and Fgf10 is a negative regulator of postnatal hypothalamic neurogenesis.
引用
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页数:12
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