Unique contribution of heat shock transcription factor 4 in ocular lens development and fiber cell differentiation

Jin Na Min, Yan Zhang, Demetrius Moskophidis, Nahid F. Mivechi

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Mammalian ocular lens development results via a differentiation program that is highly regulated by tissue-specific transcription factors. Central to this is the terminal differentiation of fiber cells, which develop from epithelial cells on the anterior surface of the lens, accompanied by a change in cell shape and expression of structural proteins (such as membrane proteins MP19, MIP26, connexin 43, 46, and 50, cytoskeletal proteins CP49, CP115, and α, β, and γ crystallins), creating a transparent, refractive index gradient in the lens. Mutations in genes controlling eye development and in lens structural protein genes are associated with multiple ocular developmental disorders, including cataracts and other opacities of the lens. Here we show that heat shock transcription factor 4 (HSF4) expression in the developing lens is required for correct lens development and that inactivation of hsf4 leads to early postnatal cataract formation with primary effects specific to terminal fiber cell differentiation. These data suggest that HSF4 acts as a critical transcription factor for lens-specific target gene expression, in particular regulating the small 25 kDa heat shock protein that acts as a modifier for lens opacity and cataract development. Thus, HSF4 fulfills a central role in controlling spatial and temporal expression of genes critical for correct development and function of the lens.

Original languageEnglish (US)
Pages (from-to)205-217
Number of pages13
JournalGenesis
Volume40
Issue number4
DOIs
StatePublished - Dec 1 2004

Keywords

  • Cataract
  • Eye development
  • HSP25
  • Hsf4
  • Targeted mutation

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

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