REGIONAL DIFFERENTIATION DURING FOREBRAIN DEVELOPMENT

描述（改编自申请人摘要）：目前尚未 已知是否诱导-当一个胚胎细胞群 影响另一个基因的表达和分化， 在哺乳动物的主要区域和途径的发展， 前脑对前脑感应的清晰理解是 这一点至关重要，因为作为其基础的分子信号通路 这一过程可能会被环境毒素，基因突变， 饮食制剂、药物和滥用药物。这项建议会 评价额鼻间感应的假设 间充质，胚胎头部的表面上皮，以及 前脑神经上皮是形态发生和分化的基础 整个前脑的功能分区嗅球 以及其主要的神经支配来源-嗅上皮。的 研究者将确定间充质细胞之间的相互作用 和邻近的前脑或表面上皮细胞是必要的， 脑缺血再灌注损伤中的基因表达模式和神经元分化 推测的嗅觉上皮和前脑。的贡献 将评估四种已建立的诱导性信号分子。 维甲酸（RA），音刺猬（shh），成纤维细胞生长因子8 （FGF 8）和骨形态发生蛋白4（BMP 4）都存在于不连续的 前脑中或周围的细胞群，表面上皮和 间充质调查人员将分析是否推定 嗅觉上皮或额鼻间充质提供独特的信号 启动嗅觉结构的形态发生和分化。 最后，他将评估归纳相互作用 影响轴突投射的初始模式， 嗅上皮和前脑。因此，这些实验将 在区域和区域性期间确定细胞和分子基础， 在哺乳动物前脑的通路发展。结果将 确定发育中的前脑的主要脆弱点， 一系列环境毒素、药理学试剂和遗传物质 疾病这种前脑早期诱导的中断 发展可能最终会损害独特的行为和 属于不同前脑区域的认知功能 和电路。

DESCRIPTION (Adapted from applicant's abstract): It is not currently known whether induction-which occurs when one embryonic cell group influences gene expression and differentiation in another, plays a role in the development of major regions and pathways in the mammalian forebrain. A clear understanding of induction in the forebrain is crucial since the molecular signaling pathways that underlie this process may be disrupted by environmental toxins, genetic mutations, dietary agents, pharmaceuticals, and drugs of abuse. This proposal will evaluate the hypothesis that induction between the frontonasal mesenchyme, the surface epithelium of the embryonic head, and the forebrain neuroepithelium underlies morphogenesis and differentiation of an entire functional subdivision of the forebrain-the olfactory bulb- as well as its major source of innervation-the olfactory epithelium. The investigator will determine whether interactions between the mesenchyme and the adjacent forebrain or surface epithelia are necessary for patterned gene expression and neuronal differentiation in the presumptive olfactory epithelium and forebrain. The contributions of four established inductive signaling molecules will be assessed. Retinoic Acid (RA), sonic hedgehog (shh), Fibroblast Growth Factor 8 (FGF8) and Bone Morphogenetic Protein 4 (BMP4) are all found in discrete cell populations in or around the forebrain, surface epithelium and mesenchyme. The investigator will analyze whether the presumptive olfactory epithelium or frontonasal mesenchyme provide unique signals to initiate morphogenesis and differentiation of olfactory structures. Finally, he will evaluate the extent to which inductive interactions influence the initial patterning of axonal projections between the olfactory epithelium and the forebrain. These experiments will therefore define a cellular and molecular basis for induction during regional and pathway development in the mammalian forebrain. The results will identify a major point of vulnerability of the developing forebrain to a range of environmental toxins, pharmacological agents, and genetic diseases. Such disruptions of early induction during forebrain development may ultimately compromise the unique behavioral and cognitive functions that are the province of distinct forebrain regions and circuits.