SITE-SPECIFIC MALFORMATIONS IN THE MOUSE EMBRYO

拟议的研究将检验工作假设，即 神经递质5-羟色胺(5-羟色胺)是一种形态发生信号。 通过激活特定受体和信号来实现颅面发育 调控细胞增殖、迁移和转移的信号转导机制 其他形态调节分子的表达。5-羟色胺能调节 两种生长因子(S-100β、胰岛素样生长因子-II)与黏附相关分子 Tenascin将在下颌骨微团培养和 用定量原位杂交和免疫结合技术检测外植体 检测，并与软骨核心蛋白进行比较，软骨核心蛋白是 软骨生成。5-羟色胺表达结构对形态发生的影响 受体和形态调节分子(如Meckel‘s软骨、牙齿 细菌)将在下颌外植体中进行研究。潜在的机制 5-羟色胺对脑神经迁移的剂量依赖性刺激作用 将使用已建立的细胞迁移试验对CREST进行研究。这个 选择性受体激动剂促进迁移的能力将是 S-100β(钙)对神经脊表达影响的比较 结合蛋白)和Tenascin。细胞的5-羟色胺能调节 神经棘和下颌骨中的增殖和第二信使 用~3H-胸腺嘧啶核苷掺入、cAMP和PI测定培养物 水解度分析。这些研究与唐氏症的病因学有关 发生特征性颅面畸形的综合征，水平 S-100β和胰岛素样生长因子-II升高，血清素能机制 被更改了。这项工作也可能提供关于致畸的信息 孕期5-羟色胺能药物的潜力。

The proposed studies will test the working hypothesis that the neurotransmitter serotonin (5-HT) acts as a morphogenetic signal during craniofacial development by activation of specific receptors and signal transduction mechanisms that regulate cell proliferation, migration and expression of other morphoregulatory molecules. Serotonergic regulation of two growth factors (S-100beta, IGF-II) and the adhesion-related molecule tenascin will be investigated in mandibular micromass cultures and explants using quantitative in situ hybridization and immunobinding assays, and compared to cartilage core protein, a marker of chondrogenesis. Effects on morphogenesis of structures expressing 5-HT receptors and morphoregulatory molecules (e.g., Meckel's cartilage, tooth germ) will be studied in mandibular explants. Mechanisms underlying the dose-dependent stimulatory effects of 5-HT on migration of cranial neural crest will be studied using an established cell migration assay. The ability of selective receptor agonists to promote migration will be compared to effects on neural crest expression of S-100beta (a calcium binding protein) and tenascin. Serotonergic regulation of cell prolIferation and second messengers in neural crest and mandibular cultures will be determined using 3H-thymidine incorporation, cAMP, and PI hydrolysis assays. These studies are relevant to the etiology of Down's syndrome where characteristic craniofacial malformations occur, levels of S-100beta and IGF-II are elevated, and Serotonergic mechanisms are altered. This work may also provide information regarding the teratogenic potential of Serotonergic drugs during pregnancy.