The Second Wave of Neurogenesis in the DRG

描述（由申请人提供）：成熟背根神经节（DRG）是除神经胶质细胞外约20种不同类型感觉神经元的异质混合物。这些不同的细胞类型从神经嵴衍生出来的机制仍然不完全清楚。在DRG中有两个神经发生波。第一波的祖细胞是迁移的神经嵴细胞，其沿其腹侧迁移路径沿着停止、合并并分化成本体感受神经元和机械感受神经元。第二波主要由TrkA+的伤害性传入组成，在神经嵴迁移停止后产生。最初，TrkA+神经元分散在整个新生DRG中，但在3天内，它们变得明显局限于神经节的背内侧2/3。调节这种空间隔离的机制根本不清楚。此外，引起第二次浪潮的祖先人口仍然不明确。该提案的目标是识别和表征在神经发生的第二波期间产生神经元的祖细胞，并通过延时共聚焦显微镜成像，伤害感受神经元在成熟DRG内分化时的出生和行为。

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.