Behnan Scott M, Guo Chiao, Gong Tzy-Wen, Shum Lillian, Gong Siew-Ging
School of Dentistry, University of Michigan, 1011 N. University Avenue, Ann Arbor, MI 48109-1078, USA.
Differentiation. 2005 Jun;73(5):233-9. doi: 10.1111/j.1432-0436.2005.00022.x.
The molecular mechanisms by which the primordia of the midface grow and fuse to form the primary palate are not well characterized. This is in spite of the fact that failure of growth and/or fusion of these facial primordia leads to the common human craniofacial birth defects, clefts of the lip with or without clefts of the palate. Members of the transforming growth factor beta (Tgfbeta) superfamily have been shown to play critical roles during craniofacial development. Specifically, the role of Tgfbeta-3 in mediating the fusion of the embryonic secondary palatal shelves is well documented. In a screen for genes expressed during fusion of the murine midfacial processes, Tgfbeta2 was identified as a gene differentially expressed during fusion of the lateral and medial nasal processes. The objective of our study was to analyze the spatial and temporal expression of Tgfbeta2 during critical stages of midfacial morphogenesis at both the transcript and protein levels. We also compared the pattern of expression of Tgfbeta2 with that of Bmp4, a gene shown previously to be involved in mediating the fusion process in the midface. Our results showed Tgfbeta2 expression in a very restrictive area of the epithelial layer along the borders of the midfacial primordia, in a pattern very similar to that of Bmp4. The highly restrictive and spatial and temporal pattern of expression of Tgfbeta2 implicates its role in mediating the fusion of the midfacial processes, possibly through interacting with Bmp4 in the regulation of apoptosis and/or epithelial-mesenchymal transformation. A greater understanding of the role of this gene will clarify how the normal midface grows and the mechanisms behind cleft development.
中面部原基生长并融合形成原发腭的分子机制尚未得到充分阐明。尽管这些面部原基的生长和/或融合失败会导致常见的人类颅面先天性缺陷，即唇裂伴或不伴腭裂。转化生长因子β（Tgfbeta）超家族的成员已被证明在颅面发育过程中起关键作用。具体而言，Tgfbeta-3在介导胚胎次生腭板融合中的作用已有充分记录。在一项对小鼠中面部过程融合期间表达的基因进行的筛选中，Tgfbeta2被鉴定为在外侧和内侧鼻突融合期间差异表达的基因。我们研究的目的是在转录本和蛋白质水平上分析中面部形态发生关键阶段Tgfbeta2的时空表达。我们还将Tgfbeta2的表达模式与Bmp4的表达模式进行了比较，Bmp4是一个先前已被证明参与介导中面部融合过程的基因。我们的结果显示，Tgfbeta2在沿中面部原基边界的上皮层的一个非常局限的区域表达，其模式与Bmp4非常相似。Tgfbeta2高度局限的时空表达模式表明其在介导中面部过程融合中发挥作用，可能是通过在细胞凋亡和/或上皮-间充质转化的调节中与Bmp4相互作用。对该基因作用的更深入了解将阐明正常中面部的生长方式以及腭裂发育背后的机制。
