Neural induction and patterning in vertebrates are regulated during early development by several morphogens, such as bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs). Ventral ectoderm differentiates into epidermis in response to BMPs, whereas BMP signaling is tightly inhibited in the dorsal ectoderm which develops into neural tissues. Here, we show that Cdc2-like kinase 2 (Clk2) promotes early neural development and inhibits epidermis differentiation in Xenopus embryos. clk2 is specifically expressed in neural tissues along the anterior-posterior axis during early Xenopus embryogenesis. When overexpressed in ectodermal explants, Clk2 induces the expression of both anterior and posterior neural marker genes. In agreement with this observation, overexpression of Clk2 in whole embryos expands the neural plate at the expense of epidermal ectoderm. Interestingly, the neural-inducing activity of Clk2 is increased following BMP inhibition and activation of the FGF signaling pathway in ectodermal explants. Clk2 also downregulates the level of p-Smad1/5/8 in cooperation with BMP inhibition, in addition to increasing the level of activated MAPK together with FGF. These results suggest that Clk2 plays a role in early neural development of Xenopus possibly via modulation of morphogen signals such as the BMP and FGF pathways.

中文翻译：

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Cdc2样激酶2（Clk2）促进非洲爪蟾胚胎的早期神经发育。

在脊椎动物的早期发育过程中，其神经诱导和模式受几种形态发生因子（例如骨形态发生蛋白（BMP）和成纤维细胞生长因子（FGF））的调控。腹外胚层响应BMPs分化成表皮，而BMP信号在发育成神经组织的背外胚层中受到严格抑制。在这里，我们显示Cdc2样激酶2（Clk2）促进早期的神经发育并抑制非洲爪蟾胚胎中的表皮分化。clk2在早期非洲爪蟾胚胎发生过程中沿前后轴在神经组织中特异性表达。当在外胚层外植体中过表达时，Clk2诱导前后神经标记基因的表达。与这个观察一致，整个胚胎中Clk2的过度表达以表皮外胚层为代价扩展了神经板。有趣的是，在外胚层外植体中，BMP抑制和FGF信号通路的激活后，Clk2的神经诱导活性增加。除了增加激活的MAPK和FGF的水平外，Clk2还与BMP抑制一起下调p-Smad1 / 5/8的水平。这些结果表明，Clk2在非洲爪蟾的早期神经发育中可能通过调节形态发生子信号（例如BMP和FGF途径）发挥作用。除了增加活化的MAPK和FGF的水平。这些结果表明，Clk2在非洲爪蟾的早期神经发育中可能通过调节形态发生子信号（例如BMP和FGF途径）发挥作用。除了增加活化的MAPK和FGF的水平。这些结果表明，Clk2在非洲爪蟾的早期神经发育中可能通过调节形态发生子信号（例如BMP和FGF途径）发挥作用。