Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity
Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity
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DOI：
10.1016/s0092-8674(03)00045-x
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发表时间：
2003-02-07
期刊：
影响因子：
64.5
通讯作者：
Holdener, BC
中科院分区：
文献类型：
--
作者：
Hsieh, JC;Lee, L;Holdener, BC
多细胞生物的胚胎极性和模式形成需要来自邻近细胞的感应信号。了解这些相互作用的一种方法是研究破坏发育的突变。在这里，我们证明了mesd，一个在小鼠7号染色体上的中胚层发育（mesd）缺失间隔中发现的基因，对胚胎极性和中胚层诱导的规范是必不可少的。MESD在内质网中作为LRP5和LRP6的特异性伴侣起作用，LRP5和LRP6与frizzed一起是典型WNT信号转导的辅助受体。中胚层缺陷胚胎的极性破坏和中胚层分化可能是由WNT信号的主要缺陷引起的。然而，MESD缺陷和wnt3（-/-）胚胎之间的表型差异表明，MESD可能对低密度脂蛋白受体（LDLR）家族的相关成员起作用，该家族的成员介导从货物运输到信号传导的多种细胞过程。
Specification of embryonic polarity and pattern formation in multicellular organisms requires inductive signals from neighboring cells. One approach toward understanding these interactions is to study mutations that disrupt development. Here, we demonstrate that mesd, a gene identified in the mesoderm development (mesd) deletion interval on mouse chromosome 7, is essential for specification of embryonic polarity and mesoderm induction. MESD functions in the endoplasmic reticulum as a specific chaperone for LRP5 and LRP6, which in conjunction with Frizzled, are coreceptors for canonical WNT signal transduction. Disruption of embryonic polarity and mesoderm differentiation in mesd-deficient embryos likely results from a primary defect in WNT signaling. However, phenotypic differences between mesd-deficient and wnt3(-/-) embryos suggest that MESD may function on related members of the low-density lipoprotein receptor (LDLR) family, whose members mediate diverse cellular processes ranging from cargo transport to signaling.