SITE-SPECIFIC MALFORMATIONS IN THE MOUSE EMBRYO

本研究的目的是研究血清素（5-HT） 在小鼠颅面发育和评估致畸潜力 的药物。 我们将调查5- HT及其结合蛋白（5-羟色胺结合蛋白，SBP）和受体在 上皮和间充质的颅面区域使用光和 电子显微镜技术。 5-HT对增殖的直接作用， 神经嵴源性的迁移和软骨分化 间充质将在细胞培养中使用多种细胞和 分子技术 我们还将分析5-HT或相关药物的作用 对颅神经褶皱的神经上皮细胞增殖的影响， 下面的间充质和颅面区域的上皮中。 将使用全胚胎培养来确定剂量-反应关系 和5-HT产生发育缺陷的关键暴露期 摄取抑制剂和受体类似物。 这些研究将有助于我们 了解5-HT在形态发生中的功能重要性 一般而言，并将具体说明其在上皮间充质中的作用， 颅面区域的相互作用。

The purpose of this research program is to study roles for serotonin (5-HT) in mouse craniofacial development and to assess the teratogenic potential of serotonergic drugs. We will investigate possible sites of action of 5- HT, its binding protein (serotonin binding protein, SBP) and receptors in epithelial and mesenchyme of the craniofacial region using light and electron microscopic techniques. Direct effects of 5-HT on proliferation, migration and chondrogenic differentiation of neural crest-derived mesenchyme will be studied in cell culture using a variety of cellular and molecular techniques. We will also analyze effects of 5-HT or related drug on cell proliferation in the neuroepithelium of the cranial neural folds, the underlying mesenchyme, and in epithelia of the craniofacial region. Whole embryo culture will be used to determine dose-response relationships and critical periods of exposure for developmental defects produced by 5-HT uptake inhibitors and receptor analogs. These studies will aid in our understanding of the functional importance of 5-HT in morphogenesis generally and will specifically address it role in epithelial-mesenchyme interactions of the developing craniofacial region.