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Lmx1a对发育中脊髓顶板形成的调控。

Control of roof plate formation by Lmx1a in the developing spinal cord.

作者信息

Chizhikov Victor V, Millen Kathleen J

机构信息

Department of Human Genetics, University of Chicago, 920 East 58th Street, CLSC 319, Chicago, IL 60637, USA.

出版信息

Development. 2004 Jun;131(11):2693-705. doi: 10.1242/dev.01139.

Abstract

Numerous studies have identified the roof plate as an embryonic signaling center critical for dorsal central nervous system patterning, but little is known about mechanisms that control its formation and its separation from clonally related neural crest cells and dI1 sensory interneurons. We demonstrate that the LIM homeodomain transcription factor, Lmx1a, mutated in the dreher mouse, acts to withdraw dorsal spinal cord progenitors from the cell cycle and simultaneously direct their differentiation into functional roof plate cells. Lmx1a cell-autonomously represses the dI1 progenitor fate, distinguishing the roof plate and dI1 interneuron programs, two major developmental programs of the dorsal neural tube. Lmx1a is not directly involved in neural crest development. We establish that Bmp signaling from epidermal ectoderm is necessary and sufficient for inducing Lmx1a and other co-factors that also regulate the extent of roof plate induction. We conclude that Lmx1a controls multiple aspects of dorsal midline patterning and is a major mediator of early Bmp signaling in the developing spinal cord.

摘要

众多研究已确定顶板是对背侧中枢神经系统模式形成至关重要的胚胎信号中心,但对于控制其形成以及它与克隆相关的神经嵴细胞和dI1感觉中间神经元分离的机制却知之甚少。我们证明,在德雷尔小鼠中发生突变的LIM同源域转录因子Lmx1a,可促使背侧脊髓祖细胞退出细胞周期,并同时引导它们分化为功能性顶板细胞。Lmx1a以细胞自主方式抑制dI1祖细胞命运,从而区分顶板和dI1中间神经元程序,这是背侧神经管的两个主要发育程序。Lmx1a不直接参与神经嵴发育。我们确定,来自表皮外胚层的Bmp信号对于诱导Lmx1a和其他也调节顶板诱导程度的辅助因子是必要且充分的。我们得出结论,Lmx1a控制背侧中线模式形成的多个方面,并且是发育中的脊髓中早期Bmp信号的主要介导者。

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