PUBLICATION

Multiple functions of LIM domain-binding CLIM/NLI/Ldb cofactors during zebrafish development

Authors
Becker, T., Ostendorff, H., Bossenz, M., Schlüter, A., Becker, C.G., Peirano, R.I., and Bach, I.
ID
ZDB-PUB-020912-7
Date
2002
Source
Mechanisms of Development   117(1-2): 75-85 (Journal)
Registered Authors
Becker, Catherina G., Becker, Thomas
Keywords
LIM homeodomain factor; CLIM/NLI/Ldb cofactor; eye; midbrain-hindbrain boundary; axonal projection; zebrafish
MeSH Terms
  • Animals
  • Axons/metabolism
  • Axons/ultrastructure
  • Brain/embryology
  • Brain/metabolism
  • Eye/embryology
  • Eye/metabolism
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Neurons/metabolism
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
PubMed
12204249 Full text @ Mech. Dev.
Abstract
The crucial involvement of CLIM/NLI/Ldb cofactors for the exertion of the biological activity of LIM homeodomain transcription factors (LIM-HD ) has been demonstrated. In this paper we show that CLIM cofactors are widely expressed during zebrafish development with high protein levels in specific neuronal cell types where LIM-HD proteins of the Isl class are synthesized. The overexpression of a dominant-negative CLIM molecule (DN-CLIM) that contains the LIM interaction domain (LID) during early developmental stages of zebrafish embryos results in an impairment of eye and midbrain-hindbrain boundary (MHB) development and disturbances in the formation of the anterior midline. On a cellular level we show that the outgrowth of peripheral but not central axons from Rohon Beard (RB) and trigeminal sensory neurons is inhibited by DN-CLIM overexpression. We demonstrate a further critical role of CLIM cofactors for axonal outgrowth of motor neurons. Additionally, DN-CLIM overexpression causes an increase of Isl-protein expression levels in specific neuronal cell types, likely due to a protection of the DN-CLIM/ LIM-HD complex from proteasomal degradation. Our results demonstrate multiple roles of the CLIM cofactor family for the development of entire organs, axonal outgrowth of specific neurons and protein expression levels.
Genes / Markers
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Human Disease / Model
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Fish
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Mapping