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首页> 外文期刊>Biology Open >Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism
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Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism

机译：融合抑制基因通过Gli3依赖性机制调节出生后神经干细胞和前体细胞的增殖

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The ventricular-subventricular zone (V-SVZ) of the forebrain is the source of neurogenic stem/precursor cells for adaptive and homeostatic needs throughout the life of most mammals. Here, we report that Suppressor of Fused (Sufu) plays a critical role in the establishment of the V-SVZ at early neonatal stages by controlling the proliferation of distinct subpopulations of stem/precursor cells. Conditional deletion of Sufu in radial glial progenitor cells (RGCs) at E13.5 resulted in a dramatic increase in the proliferation of Sox2+ Type B1 cells. In contrast, we found a significant decrease in Gsx2+ and a more dramatic decrease in Tbr2+ transit amplifying cells (TACs) indicating that innate differences between dorsal and ventral forebrain derived Type B1 cells influence Sufu function. However, many precursors accumulated in the dorsal V-SVZ or failed to survive, demonstrating that despite the over-proliferation of Type B1 cells, they are unable to transition into functional differentiated progenies. These defects were accompanied by reduced Gli3 expression and surprisingly, a significant downregulation of Sonic hedgehog (Shh) signaling. Therefore, these findings indicate a potential role of the Sufu-Gli3 regulatory axis in the neonatal dorsal V-SVZ independent of Shh signaling in the establishment and survival of functional stem/precursor cells in the postnatal dorsal V-SVZ.
机译：前脑的心室-室下区（V-SVZ）是神经源性干/前体细胞的来源，在大多数哺乳动物的一生中，这些细胞都具有适应性和体内稳态的需求。在这里，我们报告说，融合抑制基因（Sufu）通过控制干/前体细胞不同亚群的增殖，在新生儿早期V-SVZ的建立中起着关键作用。 E13.5处的放射状神经胶质祖细胞（RGC）中有条件的Sufu的缺失导致Sox2 + B1型细胞的增殖急剧增加。相反，我们发现Gsx2 +的显着减少和Tbr2 +转运放大细胞（TACs）的显着减少，表明背侧和腹侧前脑来源的B1型细胞之间的先天差异会影响Sufu功能。然而，许多前体积累在背侧V-SVZ中或未能存活，这表明尽管B1型细胞过度增殖，但它们仍无法转变为功能分化的后代。这些缺陷伴随着Gli3表达的降低，以及令人惊讶的是，声波刺猬（Shh）信号的显着下调。因此，这些发现表明，Sufu-Gli3调控轴在新生背V-SVZ中独立于Shh信号在新生背V-SVZ的功能性干/前体细胞的建立和存活中具有潜在作用。

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