Notch signaling is required to maintain all neural stem cell populations - Irrespective of spatial or temporal niche

被引:91
作者
Alexson, TO
Hitoshi, S
Coles, BL
Bernstein, A
van der Kooy, D
机构
[1] Univ Toronto, Dept Med Biophys, Neurobiol Res Grp, Toronto, ON M5S 1A8, Canada
[2] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
[3] Natl Inst Physiol Sci, Div Neurobiol & Bioinformat, Aichi, Japan
关键词
presenilin; retinal stem cell; self-renewal; symmetric division; asymmetric division; cell cycle time;
D O I
10.1159/000090751
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Recently, Notch signaling has been reported to underscore the ability of neural stem cells (NSCs) to self-renew. Utilizing mice deficient in presenilin-1 (PS1), we asked whether the function of Notch signaling in NSC maintenance was conserved. At embryonic day 14.5, all NSCs - both similar (cortex-, ganglionic eminence- and hindbrain-derived) and distinct (retinal stem cell) - require Notch signaling in a gene-dosage-sensitive manner to undergo expansionary symmetric divisions, as assessed by the clonal, in vitro neurosphere assay. Within the adult, however, Notch signaling modulates cell cycle time in order to ensure brain-derived NSCs retain their self-renewal property. At face value, the effects in the embryo and adult appear different. We propose potential hypotheses, including the ability of cell cycle to modify the mode of division, in order to resolve this discrepancy. Regardless, these findings demonstrate that PS1, and presumably Notch signaling, is required to maintain all NSCs.
引用
收藏
页码:34 / 48
页数:15
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