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First published online October 9, 2009
doi: 10.1242/10.1242/dev.042242

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Cdc42- and IRSp53-dependent contractile filopodia tether presumptive lens and retina to coordinate epithelial invagination

¹ The Visual Systems Group, Children's Hospital Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
² Division of Pediatric Ophthalmology, Children's Hospital Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
³ IFOM Foundation, Institute FIRC of Molecular Oncology, University of Milan, School of Medicine, Dpt. San Paolo, Via Adamello, 16 20139 Milano, Italy.
⁴ Department of Ophthalmology, University of California San Francisco, San Francisco, CA 94122, USA.
⁵ Fraunhofer Institute for Cell Therapy and Immunology - IZI, Deutscher Platz 5e, 04103 Leipzig, Germany.
⁶ Department of Chemistry and Physics, Lamar University, Beaumont, TX 77710, USA.
⁷ Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
⁸ Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
⁹ Department of Ophthalmology, University of Cincinnati, Cincinnati, OH 45229, USA.

^* Author for correspondence (Richard.Lang{at}cchmc.org)

Accepted 2 September 2009

The vertebrate lens provides an excellent model with which to study the mechanisms required for epithelial invagination. In the mouse, the lens forms from the head surface ectoderm. A domain of ectoderm first thickens to form the lens placode and then invaginates to form the lens pit. The epithelium of the lens placode remains in close apposition to the epithelium of the presumptive retina as these structures undergo a coordinated invagination. Here, we show that F-actin-rich basal filopodia that link adjacent presumptive lens and retinal epithelia function as physical tethers that coordinate invagination. The filopodia, most of which originate in the presumptive lens, form at E9.5 when presumptive lens and retinal epithelia first come into close contact, and have retracted by E11.5 when invagination is complete. At E10.5 - the lens pit stage - there is approximately one filopodium per epithelial cell. Formation of filopodia is dependent on the Rho family GTPase Cdc42 and the Cdc42 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 inter-epithelial distance. These data suggest that the lens-retina inter-epithelial filopodia are a fine-tuning mechanism to assist in lens pit invagination by transmitting the forces between presumptive lens and retina. Although invagination of the archenteron in sea urchins and dorsal closure in Drosophila are known to be partly dependent on filopodia, this mechanism of morphogenesis has not previously been identified in vertebrates.

Key words: Cdc42, IRSp53 (Baiap2), Eye development, Filopodia, Lens development, Morphogenesis, Mouse

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