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Regulation of mouse lens fiber cell development and differentiation by the Maf gene

Ring, Brian Z., Cordes, Sabine P., Overbeek, Paul A., Barsh, Gregory S.·2000·Development
DOI 10.1242/dev.127.2.307
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Abstract

Maf is a basic domain/leucine zipper domain protein originally identified as a proto-oncogene whose consensus target site in vitro, the T-MARE, is an extended version of an AP-1 site normally recognized by Fos and Jun. Maf and the closely related family members Neural retina leucine zipper (Nrl), L-Maf, and Krml1/MafB have been implicated in a wide variety of developmental and physiologic roles; however, mutations in vivo have been described only for Krml1/MafB, in which a loss-of-function causes abnormalities in hindbrain development due to failure to activate the Hoxa3 and Hoxb3 genes. We have used gene targeting to replace Maf coding sequences with those of lacZ, and have carried out a comprehensive analysis of embryonic expression and the homozygous mutant phenotype in the eye. Maf is expressed in the lens vesicle after invagination, and becomes highly upregulated in the equatorial zone, the site at which self-renewing anterior epithelial cells withdraw from the cell cycle and terminally differentiate into posterior fiber cells. Posterior lens cells in MaflacZmutant mice exhibit failure of elongation at embryonic day 11.5, do not express αA-and all of the β-crystallin genes, and display inappropriately high levels of DNA synthesis. This phenotype partially overlaps with those reported for gene targeting of Prox1 and Sox1; however, expression of these genes is grossly normal, as is expression of Eya1, Eya2, Pax6, and Sox2. Recombinant Maf protein binds to T-MARE sites in the αA-, βB2-, and βA4-crystallin promoters but fails to bind to a point mutation in the αA-crystallin promoter that has been shown previously to be required for promoter function. Our results indicate that Maf directly activates many if not all of the β-crystallin genes, and suggest a model for coordinating cell cycle withdrawal with terminal differentiation.

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Metadata

Authors
Ring, B. Z., Cordes, S. P., Overbeek, P. A., & Barsh, G. S.
Affiliations
  • Departments of Pediatrics and Genetics and the Howard Hughes Medical Institute 1 , Beckman Center, Stanford, California 94305-5428, USA
  • Department of Cell Biology 2 , Baylor College of Medicine, Houston, TX 77030, USA
Venue
Development
Publisher
The Company of Biologists
Published
2000-01-15
Volume
127
Issue
2
Pages
307-317
ISSN
  • 0950-1991
  • 1477-9129
DOI
10.1242/dev.127.2.307
Cited by
194
References
0
Language
en

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CoChat. (2026). Citation check: Regulation of mouse lens fiber cell development and differentiation by the Maf gene. https://app.cochat.ai/papers/10.1242/dev.127.2.307
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Ring, B. Z., Cordes, S. P., Overbeek, P. A., & Barsh, G. S. (2000). Regulation of mouse lens fiber cell development and differentiation by the Maf gene. Development. https://doi.org/10.1242/dev.127.2.307

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