The Hippo pathway regulates axis formation and morphogenesis in Hydra.

The Hippo pathway regulates axis formation and morphogenesis in Hydra.
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DOI:
10.1073/pnas.2203257119
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发表时间:
2022-07-19
影响因子:
11.1
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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多细胞生物体平面图的进化是生物学中的一个中心问题。在这里,我们提供了遗传证据的参与河马级联,一个关键的生长调节途径轴形成水螅,早期出现的后生动物。我们证明,河马激酶调节雅普上游的Wnt信号在轴的形成,并表明,雅普和河马激酶途径调节细胞增殖和控制的肌动蛋白细胞骨架早在后生动物进化。根据我们的研究结果,我们推测,河马信号和核雅普担任链接连续细胞分裂,细胞密度,轴的形成早期后生动物的进化。早期后生动物有机体的细胞最初是如何组织起来形成体轴的?经典的Wnt途径已被证明是足够的诱导轴刺胞动物,一个姐妹组的两侧,是重要的两侧轴的形成。在这里,我们提供的实验证据表明,在刺胞水螅的河马途径调节形成一个新的轴在萌芽的Wnt途径的上游。Hippo通路的转录靶点,转录辅激活因子雅普,抑制水螅出芽的起始,并受水螅LATS的调节。此外,我们还展示了Hippo途径在调节水螅肌动蛋白组织和细胞增殖中的功能。我们推测,河马通路作为一个连续的细胞分裂,细胞密度,轴形成早期后生动物进化之间的联系。
The evolution of a body plan in multicellular organisms is a central problem in biology. Here, we provide genetic evidence of the involvement of the Hippo cascade, a key growth regulating pathway in axis formation in Hydra, an early emerging metazoan. We demonstrate that the Hippo kinases regulate YAP upstream of Wnt signaling in axis formation and show that YAP and Hippo kinase pathway regulation of cell proliferation and control of the actin cytoskeleton were established early in metazoan evolution. Based on our results we speculate that Hippo signaling and nuclear Yap served to link continuous cell division, cell density, and axis formation early in metazoan evolution. How did cells of early metazoan organisms first organize themselves to form a body axis? The canonical Wnt pathway has been shown to be sufficient for induction of axis in Cnidaria, a sister group to Bilateria, and is important in bilaterian axis formation. Here, we provide experimental evidence that in cnidarian Hydra the Hippo pathway regulates the formation of a new axis during budding upstream of the Wnt pathway. The transcriptional target of the Hippo pathway, the transcriptional coactivator YAP, inhibits the initiation of budding in Hydra and is regulated by Hydra LATS. In addition, we show functions of the Hippo pathway in regulation of actin organization and cell proliferation in Hydra. We hypothesize that the Hippo pathway served as a link between continuous cell division, cell density, and axis formation early in metazoan evolution.
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