Gong Siew-Gong, Guo Chiao
Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, 1011 N. University Avenue, Ann Arbor, MI 48109-1078, USA.
Differentiation. 2003 Apr;71(3):228-36. doi: 10.1046/j.1432-0436.2003.710304.x.
The molecular mechanisms by which the primordia of the midface grow and fuse to form the primary palate portion of the craniofacial region are not well characterized. This is in spite of the fact that failure of growth and/or fusion of these primordia leads to the most common craniofacial birth defect in humans (i.e. clefts of the lip and/or palate). Bmp4 plays a critical role during early embryonic development and has previously been shown to play a role in epithelial-mesenchymal interactions in the craniofacial region of chicks. We analyze the expression of bmp4 in mouse as the midfacial processes undergo fusion to form the primary palate. We show that bmp4 is expressed in a very distinct manner in the three midfacial processes (lateral nasal, LNP, medial nasal, MNP, and maxillary processes, MxP) that ultimately fuse to form the midface. Prior to fusion of the midfacial processes, bmp4 is expressed in the ectoderm of the LNP, MNP, and MxP in a distinct spatial and temporal manner near and at the site of fusion of the midface. Bmp4 appears to demarcate the cells in the LNP and MNP that will eventually contact and fuse with each other. As fusion of the three prominences proceeds, some bmp4 expressing cells are trapped in the fusion line. Later, the expression of bmp4 switches to the mesenchyme of the midface underlying its initial expression in the ectoderm. The switch occurs soon after fusion of the three processes. The pattern of expression in the midfacial region implicates the important role of bmp4 in mediating the fusion process, possibly through apoptosis of cells in the putative site of fusion, during midfacial morphogenesis.
中面部原基生长并融合形成颅面区域原腭部分的分子机制尚未得到充分阐明。尽管这些原基生长和/或融合失败会导致人类最常见的颅面出生缺陷（即唇裂和/或腭裂）。Bmp4在胚胎早期发育过程中起关键作用，此前已证明它在鸡颅面区域的上皮-间充质相互作用中发挥作用。我们分析了小鼠中面部各突起融合形成原腭时bmp4的表达情况。我们发现，bmp4在最终融合形成中面部的三个中面部突起（外侧鼻突，LNP；内侧鼻突；MNP；上颌突，MxP）中以非常独特的方式表达。在中面部突起融合之前，bmp4以独特的时空方式在LNP、MNP和MxP的外胚层中靠近中面部融合部位及融合部位表达。Bmp4似乎划分出了LNP和MNP中最终会相互接触并融合的细胞。随着三个突起的融合进行，一些表达bmp4的细胞被困在融合线中。之后，bmp4的表达切换到中面部的间充质，该间充质位于其最初在外胚层中的表达部位下方。这种切换在三个突起融合后不久发生。中面部区域的表达模式表明，bmp4在中面部形态发生过程中可能通过融合假定部位的细胞凋亡来介导融合过程，发挥着重要作用。
