cMet signaling functions during zebrafish hindbrain development

During development, cMet signaling regulates a range of cellular processes, including growth, survival and migration (Birchmeier, 2003). Human genetic studies have demonstrated a correlation between a cMET mutation and autism (Campbell et al., 2006). The cMet gene encodes a tyrosine kinase receptor, which is activated by Hgf (hepatocyte growth factor) ligand. In this study we are exploiting the advantages of the zebrafish to ask how cMet signaling functions during hindbrain development. We have analyzed cMet expression in the developing zebrafish hindbrain. We find expression in rhombomere 1 (r1; future cerebellum), and in migrating facial branchiomotor neurons (FMNs). We are in the process of identifying additional cMet-expressing neurons. Database analysis reveals two zebrafish hgf isoforms (hgf1 and hgf2). hgf1 is expressed at low levels throughout the developing hindbrain, and at high levels in migrating neural crest. We are currently analyzing hgf2 expression. Our functional analysis shows that cMet signaling is required for normal FMNs migration. Morpholino knock-down of cMet function causes major defects in FMNs migration, while Hgf1 function knock-down causes mild defects. We further find that cMet knock-down causes specific cell death, suggesting a role in cell survival. In future experiments we will establish whether cMet signaling plays roles in hindbrain neural proliferation and/or differentiation, or in migration of cerebellar neurons.