Semaphorin3A Regulates Neural Crest Migration Into the Eye During Cornea Development

Abstract

Purpose: To determine the role of lens-derived Semaphorin3A during neural crest migration into the eye. Methods: Using in situ hybridization, we characterized the expression of Semaphorin3A (Sema3A) in the eye and its receptor Neuropilin-1 (Npn-1) by neural crest cells in the periocular region during cornea development in chick embryos. Migration of neural crest cells into the eye was tracked after lens ablation or inhibition of Sema3A in the lens using quail-chick chimera technique and immunohistochemistry. Results: We show that the lens continuously expresses Sema3A during cornea development and neural crest cells express Npn-1 in the periocular region. Interestingly, only the neural crest cells that down regulate Npn-1 migrate into the eye to form the cornea. We also show that the lens, which immediately underlies the ectoderm, inhibits neural crest migration into the rudimentary eye since lensectomy results in premature migration and malformation of the cornea. Additionally, inhibiting of Sema3A signaling in the lens phenocopies lensectomy. Conclusions: Our results demonstrate that lens-derived Sema3A regulates periocular neural crest migration into the eye and is necessary for the proper formation of the cornea.

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