Zhang, Ying and Fan, Jieqing and Ho, Joshua W K and Hu, Tommy and Kneeland, Stephen C and Fan, Xueping and Xi, Qiongchao and Sellarole, Michael A and de Vries, Wilhelmine N and Lu, Weining and Lachke, Salil A and Lang, Richard A and John, Simon W M and Maas, Richard L (2016) Crim1 regulates integrin signaling in murine lens development. Development, 143. pp.356-366. ISSN 1477-9129 (OA)
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Abstract
The developing lens constitutes a powerful system for investigating the molecular basis of inductive tissue interactions and for studying cataract, the leading cause of blindness. The formation of tightly controlled cell-cell adhesions and cell-matrix junctions between lens epithelial (LE) cells, between lens fiber (LF) cells, and between these two cell populations enables the vertebrate lens to adopt its highly ordered structure and to acquire its optical transparency. Adhesion molecules are thought to maintain this ordered structure, but little is known about their identity or molecular interactions. Cysteine-rich motor neuron 1 (CRIM1), a type I transmembrane protein, is strongly expressed in the developing lens and its mutation causes ocular disease in both mice and humans. However, how Crim1 regulates lens morphogenesis is not understood. We identified a novel ENU-induced hypomorphic allele of Crim1, Crim1(glcr11), which in the homozygous state causes cataract and microphthalmia. Using this allele and two other Crim1 mutant alleles, Crim1(null) and Crim1(cko), we show that the lens defects in Crim1 mutants originate from defective LE cell polarity, proliferation and cell adhesion. The Crim1 adhesive function is likely required for interactions both between LE cells and between LE and LF cells. We further show that Crim1 acts in LE cells where it co-localizes with and regulates the levels of active β1 integrin and of phosphorylated FAK and ERK (pFAK, pERK). Lastly, the RGD and transmembrane motifs of Crim1 are required for the regulation of pFAK. These results identify an important function for Crim1 in the regulation of integrin- and FAK-mediated LE cell adhesion during lens development.
(NIH/NEI grants EY010123, NEI T32 EY714517, EY11721).
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 19 Jan 2016 04:28 |
| Last Modified: | 24 May 2016 22:30 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/190 |
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