MOLECULAR CONTROLS OF SECONDARY PALATE MORPHOGENESIS

这项研究的长期目标是检查分子 细胞上皮-间充质转化的调控机制 腭裂发生过程中的医学边缘上皮细胞(MEE)。近期 这个研究小组的成就记录了 体内和体外培养的内侧缘上皮细胞。这些研究 更确切地说，经历编程细胞的模式 死亡，与腭部融合同时发生，然而细胞仍然活着 它们经历了从上皮到间充质的表型变化。这个 转分化的MEE具有细胞增殖能力和 残留在腭部粘膜的结缔组织中。这是一项新的 观察提供了几个独特的机会来研究这两个 与MEE表型转分化相关的细胞内变化 而细胞外信号可能负责上皮细胞- 间充质转化。我们最近对人类命运的观察 在腭裂发生过程中的MEE导致了一种假说，特定的 基因表达的变化仅限于内侧边缘上皮 并与上皮间充质形成机制有关 这些细胞的转化。用来检验这一点的具体目标 假说将是：1)表征MEE的分子表型 在上皮-间充质细胞转分化过程中的作用 并将这些变化在时间上与血管的形态过程联系起来 腭裂融合，2)检测基因的表达模式 与细胞周期和它们的功能/修饰有关 与MEE增殖的分子调控相关的基因产物 上皮-间充质转化过程，3)表征 微血管内皮细胞黏附分子的表达模式 决定腭突形成与间充质相互作用的作用 细胞外基质和细胞内发生的表型变化， 4)评估由以下因素引起的分子变化： 一种发育中的形态致畸剂--维甲酸，以及这些影响 是由特定的分子受体介导的。这些研究将 有助于更好地描述分子机制 与腭部融合和MEE转分化相关，并提供 头面部出生病因学检查的分子基础 缺陷。

The long-term goal of this research is to examine the molecular mechanisms that control the epithelial-mesenchymal transformation of medical edge epithelial cells (MEE) during palatogenesis. Recent accomplishments in this research group have documented the fate of the medial edge epithelial cells both in vitro and in vivo. These studies have shown that rather that undergoing a pattern of programmed cell death, coincident with palatal fusion, the cells remain viable however they undergo a phenotypic change from epithelium to mesenchyme. The transdifferentiated MEE have the capacity for cell proliferation and remain in the connective tissue of the palatal mucosa. This new observation presents several unique opportunities for examining both the intracellular changes associated with MEE phenotypic transdifferentiation and the extracellular signals that may be responsible for epithelial- mesenchymal transformation. Our recent observations on the fate of the MEE during palatogenesis have led to the hypothesis that, Specific changes in gene expression are restricted to the medial edge epithelia and associated with the mechanism for epithelial-mesenchymal transformation of these cells. The specific aims used to examine this hypothesis will be; 1) to characterize the molecular phenotype of MEE during epithelial-mesenchymal transdifferentiation both in vitro and in vivo and relate these changes temporally to the morphologic processes of palatal fusion, 2) to examine the pattern of expression of genes associated with the cell cycle and the function/modification of their gene products to correlate molecular control of MEE proliferation with the process of epithelial-mesenchymal transformation, 3) to characterize the pattern of expression of cell adhesion molecules on the MEE during palatogenesis to determine the role of interaction with the mesenchymal extracellular matrix and the phenotypic changes that occur in the cells, 4) to evaluate the molecular alterations that result from the effects of a developmental morphogen/teratogen, retinoic acid, and how these effects are mediated by specific molecular receptors. These studies will contribute to a better characterization of the molecular mechanisms associated with palatal fusion and MEE transdifferentiation and provide a molecular basis for examinations of the etiology of craniofacial birth defects.