Differential regulation of specification and subsequent migration of neural crest progenitors

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In the trunk of avian embryos, neural crest (NC) cells successively delaminate from the neural tube (NT) for over two days. We recently uncovered that the dorsal NT is a dynamic region traversed sequentially by progenitors that colonize NC derivatives in a ventral to dorsal order (sympathetic ganglia, then Schwann cells, DRG and finally melanocytes). Hence, a dynamic spatio-temporal fate map is present already within the NT. Furthermore, we documented that premigratory cells are already restricted to generate single derivatives. What are the signals imparted by the dorsal NT compared to those provided by the migratory environment and what are their precise functions? What is the relationship between cell specification and control of subsequent migration, i.e; does the state of specification of a cell convey the receptor repertoire for precise migration and homing, or are these distinctly regulated events?. To tackle these fundamental questions, we will use two extreme paradigms, the development of the sympathetic and of the melanocyte lineages, the first and last progenitors to emigrate from the NT, and that migrate differentially along ventral vs. lateral pathways, respectively. Experiments will be performed in avian embryos using in vivo approaches in combination with molecular, microsurgical, immunohistochemical and electron microscopical techniques. Loss and gain of gene function will be executed using the tet-on/tet-off system to achieve precise spatio-temporal resolution. These studies will be significant for understanding how hierarchical decisions during neural development cooperate with pathfinding cues to allow differentiation only at the appropriate primordia.