The Second Wave of Neurogenesis in the DRG

描述（由申请人提供）：成熟的背根神经节（DRG）除了胶质细胞外，是大约20种不同类型感觉神经元的异质混合物。神经嵴中各种细胞类型的形成机制尚不完全清楚。DRG有两波神经发生。第一波的祖细胞是迁移的神经嵴细胞，它们沿着腹侧迁移路径停止，合并并分化为本体感觉神经元和机械感觉神经元。第二波主要由TrkA+的伤害性事件组成，在神经嵴迁移停止后产生。最初TrkA+神经元分散在新生DRG中，但在3天内，它们明显局限于神经节背内侧2/3。介导这种空间隔离的机制根本不为人所知。此外，导致第二波浪潮的祖先人口仍然不明确。本研究的目标是鉴定和表征在第二波神经发生过程中产生神经元的祖细胞，并通过延时共聚焦显微镜成像，在成熟的DRG中，当伤害神经元分化时，它们的产生和行为。

DESCRIPTION (provided by applicant): The mature dorsal root ganglion (DRG) is a heterogeneous mixture of ca 20 different classes of sensory neurons in addition to glial cells. The mechanisms by which this diverse array of cell types derives from the neural crest remains incompletely understood. There are two waves of neurogenesis in the DRG. Progenitors for the first wave are migrating neural crest cells that stop along their ventral migration pathway, coalesce, and differentiate into proprioceptive and mechanoceptive neurons. The second wave composed primarily of nociceptive afferents that are TrkA+, are bom after the cessation of neural crest migration. Initially TrkA+ neurons are dispersed throughout the nascent DRG, but within 3 days they become dramatically confined to the dorsal medial 2/3 of the ganglion. The mechanisms mediating this spatial segregation are not at all understood. Furthermore, the progenitor population that gives rise to the 2nd wave remains ill defined. The goals of this proposal are to identify and characterize the progenitor cells that give rise to neurons born during the 2nd wave of neurogenesis, and to image, via time-lapse confocal microscopy, the birth and behavior of nociceptive neurons as they differentiate within the maturing DRG.