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Article: Crim1 regulates integrin signaling in murine lens development

TitleCrim1 regulates integrin signaling in murine lens development
Authors
KeywordsCataract
Cell adhesion
Crim1
Cysteine-rich transmembrane BMP regulator 1
Eye development
Integrin
Lens
Mouse
Issue Date2016
PublisherThe Company of Biologists Ltd. The Journal's web site is located at https://dev.biologists.org/
Citation
Development (Cambridge), 2016, v. 143, n. 2, p. 356-366 How to Cite?
Abstract© 2016 Published by The Company of Biologists Ltd. The developing lens is 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 a highly ordered structure and acquire optical transparency. Adhesion molecules are thought to maintain this ordered structure, but little is known about their identity or 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. How Crim1 regulates lens morphogenesis is not understood. We identified a novel ENU-induced hypomorphic allele of Crim1, Crim1glcr11, which in the homozygous state causes cataract and microphthalmia. Using this and two other mutant alleles, Crim1nulland Crim1cko, we show that the lens defects in Crim1 mouse mutants originate from defective LE cell polarity, proliferation and cell adhesion. Crim1 adhesive function is likely to be required for interactions both between LE cells and between LE and LF cells. We show that Crim1 acts in LE cells, where it colocalizes with and regulates the levels of active β1 integrin and of phosphorylated FAK and ERK. The RGD and transmembrane motifs of Crim1 are required for regulating FAK phosphorylation. These results identify an important function for Crim1 in the regulation of integrin- and FAK- mediated LE cell adhesion during lens development.
Persistent Identifierhttp://hdl.handle.net/10722/262846
ISSN
2023 Impact Factor: 3.7
2023 SCImago Journal Rankings: 1.852
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Ying-
dc.contributor.authorFan, Jieqing-
dc.contributor.authorHo, Joshua W.K.-
dc.contributor.authorHu, Tommy-
dc.contributor.authorKneeland, Stephen C.-
dc.contributor.authorFan, Xueping-
dc.contributor.authorXi, Qiongchao-
dc.contributor.authorSellarole, Michael A.-
dc.contributor.authorde Vries, Wilhelmine N.-
dc.contributor.authorLu, Weining-
dc.contributor.authorLachke, Salil A.-
dc.contributor.authorLang, Richard A.-
dc.contributor.authorJohn, Simon W.M.-
dc.contributor.authorMaas, Richard L.-
dc.date.accessioned2018-10-08T02:47:15Z-
dc.date.available2018-10-08T02:47:15Z-
dc.date.issued2016-
dc.identifier.citationDevelopment (Cambridge), 2016, v. 143, n. 2, p. 356-366-
dc.identifier.issn0950-1991-
dc.identifier.urihttp://hdl.handle.net/10722/262846-
dc.description.abstract© 2016 Published by The Company of Biologists Ltd. The developing lens is 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 a highly ordered structure and acquire optical transparency. Adhesion molecules are thought to maintain this ordered structure, but little is known about their identity or 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. How Crim1 regulates lens morphogenesis is not understood. We identified a novel ENU-induced hypomorphic allele of Crim1, Crim1glcr11, which in the homozygous state causes cataract and microphthalmia. Using this and two other mutant alleles, Crim1nulland Crim1cko, we show that the lens defects in Crim1 mouse mutants originate from defective LE cell polarity, proliferation and cell adhesion. Crim1 adhesive function is likely to be required for interactions both between LE cells and between LE and LF cells. We show that Crim1 acts in LE cells, where it colocalizes with and regulates the levels of active β1 integrin and of phosphorylated FAK and ERK. The RGD and transmembrane motifs of Crim1 are required for regulating FAK phosphorylation. These results identify an important function for Crim1 in the regulation of integrin- and FAK- mediated LE cell adhesion during lens development.-
dc.languageeng-
dc.publisherThe Company of Biologists Ltd. The Journal's web site is located at https://dev.biologists.org/-
dc.relation.ispartofDevelopment (Cambridge)-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCataract-
dc.subjectCell adhesion-
dc.subjectCrim1-
dc.subjectCysteine-rich transmembrane BMP regulator 1-
dc.subjectEye development-
dc.subjectIntegrin-
dc.subjectLens-
dc.subjectMouse-
dc.titleCrim1 regulates integrin signaling in murine lens development-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1242/dev.125591-
dc.identifier.pmid26681494-
dc.identifier.scopuseid_2-s2.0-84954493023-
dc.identifier.volume143-
dc.identifier.issue2-
dc.identifier.spage356-
dc.identifier.epage366-
dc.identifier.eissn1477-9129-
dc.identifier.isiWOS:000369500200018-
dc.identifier.issnl0950-1991-

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