YAP Activity Is Necessary and Sufficient for Basal Progenitor Abundance and Proliferation in the Developing Neocortex
YAP Activity Is Necessary and Sufficient for Basal Progenitor Abundance and Proliferation in the Developing Neocortex
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DOI：
10.1016/j.celrep.2019.03.091
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发表时间：
2019-04-23
期刊：
影响因子：
8.8
通讯作者：
Huttner, Wieland B.
中科院分区：
文献类型：
--
作者：
Kostic, Milos;Paridaen, Judith T. M. L.;Huttner, Wieland B.
在哺乳动物进化过程中，新皮质的扩张与室管膜下区基底祖细胞增殖的增加有关。在这里，我们探讨了雅普，主要的下游效应的海马途径，在增殖的基础祖细胞的潜在作用。雅普的表达和活性在雪貂和人基底祖细胞中高，它们表现出高增殖能力，但在缺乏这种能力的小鼠基底祖细胞中低。在小鼠基底祖细胞中组成型活性雅普的条件性表达导致基底祖细胞增殖增加并促进上层神经元的产生。药理学和遗传学干扰雅普在雪貂和人类发育中的新皮质中的功能导致循环基础祖细胞的丰度降低。总之，我们的数据表明，雅普是必要的，足以促进基底祖细胞的增殖，并建议增加雅普水平和推测活动有助于新皮层的进化扩张。
Neocortex expansion during mammalian evolution has been linked to an increase in proliferation of basal progenitors in the subventricular zone. Here, we explored a potential role of YAP, the major down-stream effector of the Hippo pathway, in proliferation of basal progenitors. YAP expression and activity are high in ferret and human basal progenitors, which exhibit high proliferative capacity, but low in mouse basal progenitors, which lack such capacity. Conditional expression of a constitutively active YAP in mouse basal progenitors resulted in increased proliferation of basal progenitor and promoted production of upper-layer neurons. Pharmacological and genetic interference with YAP function in ferret and human developing neocortex resulted in decreased abundance of cycling basal progenitors. Together, our data indicate that YAP is necessary and sufficient to promote the proliferation of basal progenitors and suggest that increases in YAP levels and presumably activity contributed to the evolutionary expansion of the neocortex.