April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Mammalian Lens Placode Invagination Requires Cdc42, RhoA and Rac1
B. K. Chauhan; A. DiSanza; S.-Y. Choi; M. Lou; H. E. Beggs; G. Scita; Y. Zheng; R. A. Lang
Author Affiliations & Notes
  • B. K. Chauhan
    The Visual Systems Group, Division of Pediatric Ophthalmology,
    Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
    Dept. of Ophthalmology, University of Cincinnati, Cincinnati, Ohio
  • A. DiSanza
    School of Medicine Dept., IFOM Foundation, Institute FIRC of Molecular Oncology, University of Milan, San Paolo, Via Adamello, 16 20139 Milano, Italy
  • S.-Y. Choi
    University of California San Francisco, Department of Ophthalmology, San Francisco, California
  • M. Lou
    Department of Chemistry and Physics, Lamar University, Beaumont, Texas
  • H. E. Beggs
    University of California San Francisco, Department of Ophthalmology, San Francisco, California
  • G. Scita
    School of Medicine Dept., IFOM Foundation, Institute FIRC of Molecular Oncology, University of Milan, San Paolo, Via Adamello, 16 20139 Milano, Italy
  • Y. Zheng
    Division of Experimental Hematology and Cancer Biology,
    Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
  • R. A. Lang
    The Visual Systems Group, Division of Pediatric Ophthalmology,
    Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
    Dept. of Ophthalmology, University of Cincinnati, Cincinnati, Ohio
  • Footnotes
    Commercial Relationships  B.K. Chauhan, None; A. DiSanza, None; S.-Y. Choi, None; M. Lou, None; H.E. Beggs, None; G. Scita, None; Y. Zheng, None; R.A. Lang, None.
  • Footnotes
    Support  NIH Grants EY15766, EY16241, EY17848, CA131270 to R.A.L., EY0117379 to H.E.B., HL085362 to Y.Z. and the Abrahamson Pediatric Eye Institute Endowment to R.A.L.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4774. doi:
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      B. K. Chauhan, A. DiSanza, S.-Y. Choi, M. Lou, H. E. Beggs, G. Scita, Y. Zheng, R. A. Lang; Mammalian Lens Placode Invagination Requires Cdc42, RhoA and Rac1. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4774.

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Abstract

Purpose: : The formation of the mammalian lens pit provides an excellent model to study the morphogenetic pathways involved in epithelial invagination. In this study, we attempt to address the importance of three chief small Rho GTPases, Cdc42, RhoA and Rac1, in this process.

Methods: : Three conditional mouse mutants of Cdc42, RhoA and Rac1 were crossed with the le-cre mouse line to generate corresponding deleted alleles only in the induced lens ectoderm. Analysis, including immunofluorescent-staining and quantification, was conducted at specific stages of lens placode invagination.

Results: : We show that F-actin-rich filopodia link adjacent presumptive lens and retina. The filopodia, most of which originate in the presumptive lens, form at E9.5 when presumptive lens and retina first come into close contact, and have retracted by E11.5 when invagination is complete. Formation of filopodia is dependent on Cdc42 and its effector IRSp53 (Baiap2). Loss of filopodia results in reduced lens pit invagination. Pharmacological manipulation of the actin-myosin contraction pathway showed that the filopodia can respond rapidly in length to change the inter-epithelial distance.Next, we show that there are apical actomyosin complexes in the lens placode that respond to pharmalogical manipulation, thereby reducing invagination. We observe that activated myosin and F-actin is reduced in RhoA mutant lens pits, therefore producing shallower pits. In contrast, early invagination of placodes occurs in the Rac1 mutants compared to wild-types. Interestingly, the lens pits are thinner in the Rac1 mutants, but noticeably thicker for the RhoA mutants.

Conclusions: : Collectively, our results suggest that basal lens filopodia provide a physical tether that coordinates invagination and correct positioning of the lens in the early eye. The role of RhoA is to regulate the apical actomyosin complexes that drive invagination, and Rac1 is responsible for migration of the lens placode towards the presumptive retina.

Keywords: cytoskeleton • development • shape and contour 
© 2010, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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