FoxM1-driven cell division is required for neuronal differentiation in early Xenopus embryos
FoxM1-driven cell division is required for neuronal differentiation in early Xenopus embryos
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DOI：
10.1242/dev.019893
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发表时间：
2008-06
期刊：
影响因子：
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通讯作者：
Hiroyuki Ueno;N. Nakajo;Minoru Watanabe;Michitaka Isoda;N. Sagata
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文献类型：
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作者：
Hiroyuki Ueno;N. Nakajo;Minoru Watanabe;Michitaka Isoda;N. Sagata
在脊椎动物胚胎发生中，神经诱导是决定胚胎外胚层向神经外胚层命运的最早步骤。神经外胚层细胞或神经前体细胞在脱离细胞周期并分化为神经细胞之前，会积极增殖。然而，关于细胞分裂和神经分化之间的关系知之甚少，尽管在非洲爪蟾中，原肠胚形成后的细胞分裂被认为对神经分化不是必需的。在这里，我们发现叉头转录因子FoxM1是早期非洲爪蟾胚胎中神经元前体增殖和分化所必需的。FoxM1在神经外胚层表达，是该区域细胞增殖所必需的。具体来说，抑制BMP信号是神经诱导的重要步骤，可诱导FoxM1及其靶G2-M细胞周期调节因子（如Cdc25B和cyclin B3）的表达，从而促进神经外胚层的细胞分裂。此外，由FoxM1或其靶G2-M调节因子介导的G2-M细胞周期进程或细胞分裂对神经元分化至关重要，但对神经外胚层的分化并不重要。这些结果表明FoxM1在爪蟾早期胚胎中起着连接细胞分裂和神经元分化的作用。
In vertebrate embryogenesis, neural induction is the earliest step through which the fate of embryonic ectoderm to neuroectoderm becomes determined. Cells in the neuroectoderm or neural precursors actively proliferate before they exit from the cell cycle and differentiate into neural cells. However, little is known about the relationship between cell division and neural differentiation, although, in Xenopus, cell division after the onset of gastrulation has been suggested to be nonessential for neural differentiation. Here, we show that the Forkhead transcription factor FoxM1 is required for both proliferation and differentiation of neuronal precursors in early Xenopus embryos. FoxM1 is expressed in the neuroectoderm and is required for cell proliferation in this region. Specifically, inhibition of BMP signaling, an important step for neural induction, induces the expression of FoxM1 and its target G2-M cell-cycle regulators, such as Cdc25B and cyclin B3, thereby promoting cell division in the neuroectoderm. Furthermore, G2-M cell-cycle progression or cell division mediated by FoxM1 or its target G2-M regulators is essential for neuronal differentiation but not for specification of the neuroectoderm. These results suggest that FoxM1 functions to link cell division and neuronal differentiation in early Xenopus embryos.