PUBLICATION

Disruption of zebrafish somite development by pharmacologic inhibition of hsp90

Authors
Lele, Z., Hartson, S.D., Martin, C.C., Whitesell, L., Matts, R.L., and Krone, P.H.
ID
ZDB-PUB-990628-19
Date
1999
Source
Developmental Biology   210(1): 56-70 (Journal)
Registered Authors
Krone, Patrick H., Lele, Zsolt, Martin, C. Cristofre
Keywords
muscle development; zebrafish; Hsp90; geldanamycin; MyoD
MeSH Terms
  • Animals
  • Benzoquinones
  • Blotting, Western
  • Colforsin/pharmacology
  • Embryo, Nonmammalian/drug effects
  • Gene Expression Regulation, Developmental/drug effects
  • HSP90 Heat-Shock Proteins/antagonists & inhibitors*
  • Homeodomain Proteins/genetics
  • Lactams, Macrocyclic
  • Muscles/drug effects
  • Muscles/embryology
  • Nerve Tissue Proteins/genetics
  • Notochord/embryology
  • Notochord/metabolism
  • Phenotype
  • Quinones/pharmacology*
  • Somites/drug effects*
  • Zebrafish/embryology*
PubMed
10364427 Full text @ Dev. Biol.
Abstract
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 study, we have utilized the specific Hsp90-binding agent, geldanamycin, to examine the requirement for Hsp90 during zebrafish development. We show that geldanamycin interacts with both the alpha and the beta-isoforms of zebrafish 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-2-expressing muscle pioneer cells. However, early development of adaxial cells, which give rise to muscle pioneers and which strongly express the hsp90alpha gene shortly before muscle pioneer formation, appeared unaffected. Furthermore, development of the notochord, which provides many of the signals required for proper somite patterning and which does not express detectable levels of either hsp90alpha or hsp90beta mRNA, was similarly unaffected in geldanamycin-treated embryos. The data are consistent with there being a temporal and spatial requirement for Hsp90 function within somitic cells which is necessary for the formation of eng-2-expressing muscle pioneers and possibly other striated muscle fiber types.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes