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FoxA 转录因子对于背轴结构的发育至关重要。

FoxA transcription factors are essential for the development of dorsal axial structures.

机构信息

Department of Cell Biology, University of Virginia, Health Sciences Center, Charlottesville, VA 22908, USA.

出版信息

Dev Biol. 2011 Feb 15;350(2):484-95. doi: 10.1016/j.ydbio.2010.12.018. Epub 2010 Dec 21.

Abstract

In vertebrates, embryonic structures present at the dorsal midline, prechordal plate, notochord, hypochord and floor plate share a common embryonic origin. In zebrafish, they derive from a pool of progenitors located within the embryonic shield at the onset of gastrulation. The molecular mechanisms responsible for the common development of these structures remain unknown. Based on their spatial and temporal expression, transcription factors of the Forkhead box A (FoxA) family appeared to be good candidates to play such a role. In agreement with this hypothesis, we found that simultaneous knockdown of FoxA2 and FoxA3 abolish the formation of all axial derivatives, while overexpression of these transcription factors strongly enlarges dorsal mesodermal territories. We establish that, in FoxA2-FoxA3 double morphants, precursors of axial tissues are correctly induced at early gastrula stage, but their dorsal midline identity is not maintained during development and we found that progenitors of these tissues are cell-autonomously re-specified to form muscle fibers as well as cells of the ventral neural tube. Our study provides the first example of a specific loss of all dorsal midline tissues and demonstrates that members of the FoxA family have redundant functions essential to maintain the axial identity of prechordal plate, notochord, floor plate and hypochord progenitors during gastrulation.

摘要

在脊椎动物中,位于背中线、前脑板、脊索、脊索下组织和基板的胚胎结构具有共同的胚胎起源。在斑马鱼中,它们来源于胚胎盾状结构内的一群位于原肠胚形成开始时的祖细胞。负责这些结构共同发育的分子机制尚不清楚。基于它们的时空表达,叉头框 A (FoxA) 家族的转录因子似乎是发挥这种作用的良好候选者。与这一假设一致,我们发现 FoxA2 和 FoxA3 的同时敲低会消除所有轴向衍生物的形成,而这些转录因子的过表达会强烈扩大背侧中胚层区域。我们确定,在 FoxA2-FoxA3 双重突变体中,轴向组织的前体在早期原肠胚阶段被正确诱导,但它们的背中线身份在发育过程中没有得到维持,并且我们发现这些组织的祖细胞自主重新特化为形成肌肉纤维以及腹侧神经管的细胞。我们的研究提供了第一个特定的所有背中线组织丧失的例子,并证明 FoxA 家族的成员具有冗余的功能,对于维持前脑板、脊索、基板和脊索下组织祖细胞的轴向身份是必不可少的,在原肠胚形成过程中。

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