SITE-SPECIFIC MALFORMATIONS IN THE MOUSE EMBRYO

本研究计划的目的是研究5-羟色胺(5-HT)的作用。 在小鼠颅面发育中的作用并评估其致畸潜能 血清素能药物。我们将调查5个可能的行动地点- HT及其结合蛋白(5-羟色胺结合蛋白，SBP)及其受体 头面部上皮细胞和间充质细胞的光镜和组织学观察 电子显微镜技术。5-羟色胺对细胞增殖的直接作用， 神经沟来源的迁移和向软骨细胞的分化 间充质细胞将在细胞培养中使用各种细胞和 分子技术。我们还将分析5-羟色胺或相关药物的效果 关于脑神经皱褶神经上皮细胞的增殖， 在下面的间质中，以及在颅面部的上皮中。 将使用全胚胎培养来确定剂量-反应关系 5-羟色胺所致发育缺陷的暴露临界期 摄取抑制剂和受体类似物。这些研究将有助于我们 认识5-羟色胺在形态发生中的功能重要性 并将具体说明它在上皮-间充质中的作用 颅面部发育区域的相互作用。

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.