Regional morphogenesis in the hypothalamus:: a BMP-Tbx2 pathway coordinates fate and proliferation through Shh downregulation
Regional morphogenesis in the hypothalamus:: a BMP-Tbx2 pathway coordinates fate and proliferation through Shh downregulation
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DOI：
10.1016/j.devcel.2006.09.021
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发表时间：
2006-12-01
影响因子：
11.8
通讯作者：
Placzek, Marysia
中科院分区：
文献类型：
--
作者：
Manning, Liz;Ohyama, Kyoji;Placzek, Marysia
胚胎发育的一个核心挑战是了解在形态发生过程中生长和模式如何协调以指导新领域的出现。在这里，我们报道了连接细胞增殖和命运的信号级联，促进发育中的鸡下丘脑中独特祖域的形成。我们发现，在前脑底板样细胞中，Shh的下调控制着它们向一个独特的、增殖的下丘脑祖结构域的发展。Shh下调通过局部BMP-Tbx2通路发生，Tbx2作用于抑制Shh表达。我们在体内和体外实验中表明，下丘脑祖细胞中Shh的强制维持阻止了它们的正常形态发生，导致Shh受体ptc的维持，并阻止了向EmxZ(+)-增殖祖细胞状态的发展。我们的数据确定了通过BMP-Tbx2途径下调Shh的分子途径，并提供了在发育中的前脑内扩展离散祖域的机制。
A central challenge in embryonic development is to understand how growth and pattern are coordinated to direct emerging new territories during morphogenesis. Here, we report on a signaling cascade that links cell proliferation and fate, promoting formation of a distinct progenitor domain within the developing chick hypothalamus. We show that the downregulation of Shh in floor plate-like cells in the forebrain governs their progression to a distinctive, proliferating hypothalamic progenitor domain. Shh downregulation occurs via a local BMP-Tbx2 pathway, Tbx2 acting to repress Shh expression. We show in vivo and in vitro that forced maintenance of Shh in hypothalamic progenitors prevents their normal morphogenesis, leading to maintenance of the Shh receptor, ptc, and preventing progression to an EmxZ(+)-proliferative progenitor state. Our data identify a molecular pathway for the downregulation of Shh via a BMP-Tbx2 pathway and provide a mechanism for expansion of a discrete progenitor domain within the developing forebrain.