Semaphorin3A/neuropilin-1 signaling acts as a molecular switch regulating neural crest migration during cornea development
Abstract
Cranial neural crest cells migrate into the periocular region and later contribute to various ocular tissues including the cornea, ciliary body and iris. After reaching the eye, they initially pause before migrating over the lens to form the cornea. Interestingly, removal of the lens leads to premature invasion and abnormal differentiation of the cornea. In exploring the molecular mechanisms underlying this effect, we find that semaphorin3A (Sema3A) is expressed in the lens placode and epithelium continuously throughout eye development. Interestingly, neuropilin-1 (Npn-1) is expressed by periocular neural crest but down-regulated, in a manner independent of the lens, by the subpopulation that migrates into the eye and gives rise to the cornea endothelium and stroma. In contrast, Npn-1 expressing neural crest cells remain in the periocular region and contribute to the anterior uvea and ocular blood vessels. Introduction of a peptide that inhibits Sema3A/Npn-1 signaling results in premature entry of neural crest cells over the lens that phenocopies lens ablation. Furthermore, Sema3A inhibits periocular neural crest migration in vitro. Taken together, our data reveal a novel and essential role of Sema3A/Npn-1 signaling in coordinating periocular neural crest migration that is vital for proper ocular development.
Additional Information
© 2009 Elsevier. Received 2 April 2009; revised 11 September 2009; accepted 6 October 2009; available online 13 October 2009. The authors would like to thank Jonathan A. Raper for the fulllength Npn-1 cDNA and Anitha Rao for technical assistance. This work was supported in part by NIH grants EY018050 (P.Y.L.) and DE016459 (M.B.-F.). Appendix A: Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.ydbio.2009.10.008.Attached Files
Accepted Version - nihms161799.pdf
Supplemental Material - Fig._S1.jpg
Supplemental Material - Fig._S2.jpg
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Additional details
- PMCID
- PMC2800376
- Eprint ID
- 17020
- DOI
- 10.1016/j.ydbio.2009.10.008
- Resolver ID
- CaltechAUTHORS:20091222-122306746
- EY018050
- NIH
- DE016459
- NIH
- Created
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2009-12-24Created from EPrint's datestamp field
- Updated
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2021-11-08Created from EPrint's last_modified field