BHLH TRANSCRIPTION FACTORS IN NEURAL DEVELOPMENT

描述（申请人的摘要逐字复制）： 神经特异性bHLH转录因子家族，NGN 1、NGN 2、MASH 1和 MATH 1对哺乳动物神经系统的发育至关重要。这些 因子在增殖的神经前体中以精确的模式表达 在发育中的神经管中，它们的表达随着神经管的发育而消失。 细胞在有丝分裂后分化。从以前的研究来看，很明显 MASH 1和ngn 1/2在脊髓神经元内具有不同的表达结构域， 管材.然而，ngnl和ngn 2具有明显重叠的结构域，并且在 背神经管这些可能与MATH 1重叠。目前尚不清楚这些bHLH是否 因子是否共表达，或者每个因子是否标记细胞内的特定细胞类型， 重叠域。我们假设，神经前体，采取不同的 细胞命运需要bHLH因子的独特组合， 差异化和规格化。此外， 调节这类bHLH的精确时空表达 蛋白质可以控制从神经干细胞到神经干细胞的转变。 区分神经前体为了解决这些假设， 在单个细胞水平上的ngn 1、ngn 2、MATH 1和MASH 1之间的表达， 发育中的脊髓神经管，以及每个bHLH的功能要求 将确定所识别的神经元发育的因素。的 机制，以获得精确的时间和空间表达， 这些基因将被阐明，以增加对神经前体的理解。 增殖和规格化。这些实验将揭示 脊髓背角神经特异性bHLH因子的组织和作用 神经管，并进入控制神经发育的内在机制。

DESCRIPTION(Applicant's abstract reproduced verbatim): Four members of the neural specific bHLH family of transcription factors, NGN1, NGN2, MASH1 and MATH1, are essential for development of the mammalian nervous system. These factors are expressed in proliferating neural precursors in precise patterns within the developing neural tube, and their expression is extinguished as the cells become postmitotic and differentiate. From previous studies, it is clear that MASH1 and ngnl/2 have distinct expression domains within the spinal neural tube. However, ngnl and ngn2 have apparently overlapping domains, and in the dorsal neural tube these may overlap with MATH1. It is not clear if these bHLH factors are co-expressed or whether each marks a specific cell type within overlapping domains. We hypothesize that neural precursors that adopt distinct cell fates require a unique combination of bHLH factors for correct differentiation and specification. In addition, the upstream factors that regulate the precise temporal and spatial expression of this class of bHLH proteins may control the transition from a neural stem cell to a differentiating neural precursor. To address these hypotheses, the overlap of expression at a single cell level between ngnl, ngn2, MATH1, and MASH1 in the developing spinal neural tube, and the functional requirement for each bHLH factor in the development of identified neurons will be determined. The mechanisms functioning to obtain precise temporal and spatial expression of these genes will be elucidated to increase understanding into neural precursor proliferation and specification. These experiments will reveal insights into the organization and role of the neural specific bHLH factors in the spinal neural tube, and into the intrinsic mechanisms controlling neural development.