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HSF4 is required for normal cell growth and differentiation during mouse lens development
Mitsuaki Fujimoto1, Hanae Izu, Keisuke Seki
1Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Minami-Kogushi 1-1-1, Ube 755-8505, Japan.
The EMBO Journal
|October 16, 2004
Summary
Heat shock transcription factor 4 (HSF4) mutations cause cataracts by affecting gamma-crystallin and growth factor gene expression. HSF4 and HSF1 regulate cell growth and differentiation, revealing novel roles in development.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- The heat shock transcription factor (HSF) family regulates gene expression.
- HSF1 and HSF2 are implicated in developmental processes, but their mechanisms are unclear.
- The role of HSF4 in mammalian development requires elucidation.
Purpose of the Study:
- To investigate the developmental regulatory mechanisms of HSFs by studying HSF4.
- To characterize the phenotype of HSF4-null mice.
Main Methods:
- Generation and analysis of HSF4-mutant mice.
- Assessment of lens cell morphology and gene expression (gamma-crystallin, FGFs).
Main Results:
- HSF4-null mice developed cataracts with abnormal lens fiber cells and inclusion-like structures.
- Decreased gamma-crystallin expression was observed, likely causing protein instability.
- Increased proliferation and premature differentiation of lens epithelial cells correlated with elevated FGF-1, FGF-4, and FGF-7 expression.
- HSF1 competed with HSF4 for FGF gene regulation in multiple tissues.
Conclusions:
- HSF4 plays a critical role in lens development by activating gamma-crystallin genes.
- HSF4 and HSF1 collaboratively regulate growth factor gene expression, essential for cell growth and differentiation.
- These findings highlight lens-specific functions of HSF4 and the interplay between HSF1 and HSF4 in development.