STOP SIGNALS FOR NEURONAL MIGRATION IN CEREBRAL CORTEX

描述（来自申请人摘要的逐字记录）： 放射状神经胶质和其他神经基质使得能够部署准确的神经细胞。 神经元在正确的时间进入适当的位置， 与各种输入相互作用，以产生特征性的突触 哺乳动物大脑皮质的连通性和层状组织。 放射状胶质细胞和放射状胶质细胞上神经元迁移的抑制 发育导致人类神经元的异常放置和连接 大脑，一个潜在的原因，大脑疾病，如精神分裂症。因此，在本发明中， 阐明了决定神经元如何达到其适当功能的机制， 大脑皮层发育中的位置将有助于理解正常的 皮质发育以及解释各种 大脑发育障碍 研究放射状神经胶质细胞表面分子的功能， 神经元停止在适当的层状位置在发展中的大脑 皮质，我们确定了一种新的放射状胶质细胞表面分子 （放射状胶质细胞停止信号分子：RAGS 1），其时间和空间 神经元终止区域皮质发育期间的分布 它们的迁移表明，它可以作为一个位置指示器， 迁移神经元，向它们发出信号，表明它们已经到达了合适的位置。 在发育中的皮质板中的位置。在这里，我们建议阐明（1） 其功能的重要性，主要是通过研究干扰的结果， 与皮质发育过程中该分子的生物活性有关， (2)破译它的分子特征在组合中，功能和 这种放射状胶质抗原的分子特征将有助于 了解神经元-神经胶质细胞相互作用在 大脑皮层的层状组织以及破译 影响心理健康的各种发育性脑障碍的发病机制。

Description (Verbatim from the applicant's abstract): Neuronal migration on radial glia and other neural substrates enables the deployment of accurate numbers of neurons at the right time into appropriate locations, where they interact with various inputs to produce the characteristic synaptic connectivity and laminar organization of the mammalian cerebral cortex. Abnormalities in neuronal migration on radial glia, and radial glial development lead to aberrant placement and connectivity of neurons in human brain, an underlying cause of brain disorders such as schizophrenia. Thus, elucidation of mechanisms that determine how neurons reach their appropriate positions in the developing cerebral cortex would help in understanding normal cortical development as well as in deciphering the pathogenesis of various developmental brain disorders. To study radial glial cell surface molecules that function to signal cortical neurons to stop at the appropriate laminar location in the developing cerebral cortex, we identified a putatively novel radial glial cell surface molecule (Radial Glial Stop Signal molecule: RAGS 1) whose temporal and spatial distribution during cortical development in regions where neurons terminate their migration suggest that it may function as a positional indicator to migrating neurons, signaling them that they have arrived at the appropriate location in the developing cortical plate. Here, we propose to elucidate (1) its functional importance, primarily by studying the outcome of interference with the biological activity of this molecule during cortical development, and (2) decipher its molecular characteristics. In combination, the functional and molecular characterization of this radial glial antigen will help in understanding the role neuron-glial interactions play in the emergence of laminar organization of the cerebral cortex as well as in deciphering the pathogenesis of various developmental brain disorders affecting mental health.