Msx1 and Dlx5 act independently in development of craniofacial skeleton, but converge on the regulation of Bmp signaling in palate formation
Msx1 and Dlx5 act independently in development of craniofacial skeleton, but converge on the regulation of Bmp signaling in palate formation
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DOI：
10.1016/j.mod.2005.10.007
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发表时间：
2006-01-01
影响因子：
2.6
通讯作者：
Merlo, GR
中科院分区：
文献类型：
--
作者：
Levi, G;Mantero, S;Merlo, GR
Msx和Dlx同源蛋白控制颅面骨骼结构的形态发生和组织，特别是来自咽弓的结构。在体外，Msx和Dlx蛋白具有相反的转录特性，并通过其同源结构域形成异二聚体复合物，并具有相互的功能抑制。在本报告中，我们检查了Msx1的骨骼表型；D1x5双敲除（DKO）小鼠在颅面发育过程中与其表达区域的关系。D1x5和Msx1的共表达仅在胚胎组织中观察到，这些基因在胚胎组织中具有独立的功能，因此直接的蛋白质相互作用不太可能控制颅骨的形态发生。DKO颅面表型表明这些基因之间存在复杂的相互作用，或独立作用（下颌骨和中耳），或协同作用（骨组织沉积），或聚集在相同的形态发生过程（上颚生长和闭合）。在后一种情况下，DLY5的缺失部分修复了msx1依赖性上颚生长和抬高缺陷。基于这一效应，我们的数据暗示了Bmp (BmpT)/Bmp拮抗剂（Follistatin）信号：在D1x5（-/-）腭中，Bmp7和Follistatin表达水平的变化抵消了Bmp4表达的减少。这些结果强调了腭裂过程中Bmp/Bmp拮抗剂系统精确时空调控的重要性。2005爱思唯尔爱尔兰有限公司版权所有。
Msx and Dlx homeoproteins control the morphogenesis and organization of craniofacial skeletal structures, specifically those derived from the pharyngeal arches. In vitro Msx and Dlx proteins have opposing transcriptional properties and form heterodimeric complexes via their homeodomain with reciprocal functional repression. In this report we examine the skeletal phenotype of Msx1; D1x5 double knock-out (DKO) mice in relationship with their expression territories during craniofacial development. Co-expression of D1x5 and Msx1 is only observed in embryonic tissues in which these genes have independent functions, and thus direct protein interactions are unlikely to control morphogenesis of the cranium. The DKO craniofacial phenotypes indicate a complex interplay between these genes, acting independently (mandible and middle ear), synergistically (deposition of bone tissue) or converging on the same morphogenetic process (palate growth and closure). In the latter case, the absence of DLY5 rescues in part the Msx1-dependent defects in palate growth and elevation. At the basis of this effect, our data implicate the Bmp (BmpT Bmp4)/Bmp antagonist (Follistatin) signal: in the D1x5(-/-) palate changes in the expression level of Bmp7 and Follistatin counteract the reduced Bmp4 expression. These results highlight the importance of precise spatial and temporal regulation of the Bmp/Bmp antagonist system during palate closure. (c) 2005 Elsevier Ireland Ltd. All rights reserved.