Alexson Tania O, Hitoshi Seiji, Coles Brenda L, Bernstein Alan, van der Kooy Derek
Neurobiology Research Group, Department of Medical Biophysics, University of Toronto, Toronto, Canada.
Dev Neurosci. 2006;28(1-2):34-48. doi: 10.1159/000090751.
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.
最近，有报道称Notch信号通路可增强神经干细胞（NSC）的自我更新能力。我们利用早老素-1（PS1）缺陷型小鼠，探究Notch信号通路在NSC维持中的功能是否保守。在胚胎第14.5天，通过克隆性体外神经球试验评估发现，所有NSC（包括相似的，如来源于皮质、神经节隆起和后脑的NSC，以及不同的，如视网膜干细胞）都需要Notch信号通路以基因剂量敏感的方式进行扩张性对称分裂。然而，在成体中，Notch信号通路调节细胞周期时间，以确保脑源性NSC保持其自我更新特性。表面上看，胚胎期和成体期的效应似乎不同。我们提出了一些潜在的假设，包括细胞周期改变分裂模式的能力，以解决这一差异。无论如何，这些发现表明，维持所有NSC都需要PS1，可能还有Notch信号通路。
