FAW: Molecular Mechanisms of Glial-Guided Neuronal Migration

Mary Hatten博士获得了美国国家科学基金会颁发的女性科学家和工程师奖，她将继续研究中枢神经系统中神经元-神经胶质相互作用的发育机制。本研究的主要目的是通过分子生物学方法和突变小鼠模型来阐明发育中的哺乳动物大脑中神经元迁移的遗传和分子遗传调控。Hatten博士的实验室开发了小鼠小脑细胞的体外模型系统，以确定迁移的细胞和分子机制。在神经胶质引导的迁移中，将利用weaver基因表达的表型缺陷突变小鼠来分析迁移的遗传调控。一种新的粘附配体，星形胶质蛋白，已被确定介导神经元-胶质细胞结合，并将用于描述迁移的分子成分。功能研究表明，神经胶质引导的神经元迁移利用星形胶质而不是神经细胞粘附分子。该配体的表达将在其他大脑区域，如海马、皮层和皮层下区域进行检测，astrotacn cDNA将用于从其他大脑区域的cDNA文库中克隆astrotacn和相关基因。这项工作将提供星形胶质蛋白的序列、结构、功能和与已知蛋白的同源性等信息。

With a Faculty Award for Women Scientists and Engineers from the National Science Foundation, Dr. Mary Hatten will continue to study the developmental mechanisms of neuronal-glial interactions in the central nervous system. The primary goal of this research is to elucidate the genetic and molecular genetic regulation of neuronal migrations in the developing mammalian brain by employing molecular biological methods and mutant mouse models. An in vitro model system for mouse cerebellar cells has been developed in Dr. Hatten's laboratory to define the cellular and molecular mechanisms of migration. Mutant mice with phenotypic defects, expressed by the weaver gene, in glial-guided migration will be utilized to analyze the genetic regulation of migration. A novel adhesion ligand, astrotactin, has been identified to mediate neuron-glia binding and will be used to describe the molecular components of migration. Functional studies indicate that glial-guided neuronal migration utilizes astrotactin rather than neural cell adhesion molecules. The expression of this ligand will be examined in other brain regions, such as the hippocampus, cortex and subcortical regions and astrotactin cDNAs will be used to clone astrotactin and related genes from cDNA libraries of other brain regions. This work will provide information on the sequence of astrotactin, its structure, function and homology with known proteins.