Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada.
Department of Cell & Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.
Int J Mol Sci. 2021 Dec 26;23(1):229. doi: 10.3390/ijms23010229.
In mammals, the hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, orchestrating behavioral and physiological rhythms in alignment to the environmental light/dark cycle. The neurons that comprise the SCN are anatomically and functionally heterogeneous, but despite their physiological importance, little is known about the pathways that guide their specification and differentiation. Here, we report that the stem/progenitor cell transcription factor, (), is required in the embryonic SCN to control the expression of SCN-enriched neuropeptides and transcription factors. Ablation of in the developing SCN leads to downregulation of circadian neuropeptides as early as embryonic day (E) 15.5, followed by a decrease in the expression of two transcription factors involved in SCN development, and , in neonates. Thymidine analog-retention assays revealed that deficiency contributed to reduced survival of SCN neurons during the postnatal period of cell clearance, but did not affect progenitor cell proliferation or SCN specification. Our results identify SOX2 as an essential transcription factor for the proper differentiation and survival of neurons within the developing SCN.
在哺乳动物中，下丘脑视交叉上核（SCN）作为中央生物钟起搏器发挥作用，使行为和生理节律与环境的明暗周期保持一致。构成 SCN 的神经元在解剖和功能上是异质的，但尽管它们具有重要的生理意义，对于指导其特化和分化的途径知之甚少。在这里，我们报告干细胞/祖细胞转录因子（）在胚胎 SCN 中是必需的，以控制 SCN 丰富的神经肽和转录因子的表达。在发育中的 SCN 中缺失会导致早在胚胎第 15.5 天（E）时昼夜神经肽的下调，随后参与 SCN 发育的两种转录因子和的表达减少，在新生儿中也是如此。胸苷类似物保留试验表明，SCN 神经元在细胞清除的出生后期间的存活减少是由于缺乏所致，但不影响祖细胞增殖或 SCN 特化。我们的结果表明 SOX2 是发育中的 SCN 内神经元适当分化和存活所必需的转录因子。
