The Second Wave of Neurogenesis in the DRG

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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.