A Multiuse Developmental Kit

Abstract

The Kit receptor tyrosine kinase (Kit) promotes developmental processes, such as cell differentiation, migration, and survival. In zebrafish embryos lacking Kit, melanocytes fail to migrate from the dorsal neural tube during development and subsequently undergo apoptosis. The relation between these two processes--and Kit's role in each--remains unclear. Rawls and Johnson subjected zebrafish bearing a temperature-sensitive kit allele ( kit jle99 ), in which melanocytes develop normally in fish raised at 25°C but not in fish raised at 33°C, to temperature shift regimens designed to assess when during development Kit was required. At 8 days post fertilization (DPF), fish kept at 33°C until developmental stage 2 DPF (when migration has normally taken place) showed reduced melanocyte migration regardless of whether the temperature was shifted to 25°C at 2 DPF. Shifting the temperature from 33°C to 25°C at 2 DPF rescued melanocyte survival, whereas inhibiting Kit function after 2 DPF by shifting from 25°C to 33°C led to melanocyte death. Further analysis indicated that Kit function between 2 and 4 DPF was required for melanocyte survival. Phenotypic analysis of fish with kit mutations identified several mutants with selective defects in melanocyte migration and one in which migration was normal but melanocytes died. Sequence analysis indicated that migrational defects were associated with mutations in the extracellular domain, whereas the survival mutant showed a substitution in the tyrosine kinase domain. Thus, melanocyte survival is independent of migration, with both processes showing Kit dependence at different developmental stages; although Kit's tyrosine kinase activity appears important for survival, migration may involve separate Kit-dependent mechanisms. J. F. Rawls, S. L. Johnson, Temporal and molecular separation of the kit receptor tyrosine kinase's roles in zebrafish melanocyte migration and survival. Dev. Biol. 262 , 152-161 (2003). [Online Journal]