Gentic control of migration

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SF/HGF and its receptor c-met are essential for the first step in the migration of myogenic precursors, the delamination of the cells from the epithelial dermomyotome. Mice that carry mutations in the Lbx1 gene, or mutations that attenuate the c-met signaling capacity (c-methypo and Gab1) have become available. They allow delamination of the precursors, but interfere with subsequent migration. Preliminary experiments indicate that, in some respects, the Gab1 and the Lbx1 mutation have similar phenotypes. Double mutants will allow to characterize whether the two genes take over partially redundant functions. Neuregulin and its receptors, erb B2 and erb B3, are required for correct migration of neural crest cells, but not for their delamination from the neural tube. To analyze whether the cells require the signal for directed migration or for the maintenance of their migratory potential, we will express neuregulin in an autocrine manner in neural crest cells. Moreover, explant cultures will be used to study the effect of neuregulin on the migration process.