Disruption of zebrafish somite development by pharmacologic inhibition of Hsp90

Members of the Hsp90 family of molecular chaperones play important roles in allowing some intracellular signaling molecules and transcription factors to reach and maintain functionally active conformations. In the present stu dy, we have utilized the specific Hsp90-binding agent, geldanamycin, to exa mine the requirement for Hsp90 during zebrafish development. We show that g eldanamycin interacts with both the alpha and the beta-isoforms of zebrafis h Hsp90 and that geldanamycin-treated embryos consistently exhibit a number of defects in tissues which express either one of these genes. Within the somites, geldanamycin treatment results in the absence of eng-e-expressing muscle pioneer cells. However, early development of adaxial cells, which gi ve rise to muscle pioneers and which strongly express the hsp90 alpha gene shortly before muscle pioneer formation, appeared unaffected. Furthermore, development of the notochord, which provides many of the signals required f or proper somite patterning and which does not express detectable levels of either hsp90 alpha or hsp90 beta mRNA, was similarly unaffected in geldana mycin-treated embryos. The data are consistent with there being a temporal and spatial requirement for Hsp90 function within semitic cells which is ne cessary for the formation of eng-e-expressing muscle pioneers and possibly other striated muscle fiber types. (C) 1999 Academic Press.