Nephronectin-Integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal development
- Rice University, United States
Abstract
During development, cells aggregate at tissue boundaries to form normal tissue architecture of organs. However, how cells are segregated into tissue precursors remains largely unknown. Cornea development is a perfect example of this process whereby neural crest cells aggregate in the periocular region prior to their migration and differentiation into corneal cells. Our recent RNA-Seq analysis identified upregulation of Nephronectin (Npnt) transcripts during early stages of corneal development where its function has not been investigated. We found that Npnt mRNA and protein are expressed by various ocular tissues including the migratory periocular neural crest (pNC), which also express the integrin alpha 8 (Itga8) receptor. Knockdown of either Npnt or Itga8 attenuated cornea development, whereas overexpression of Npnt resulted in cornea thickening. Moreover, overexpression of Npnt variants lacking RGD binding sites did not affect corneal thickness. Neither the knockdown or augmentation of Npnt caused significant changes in cell proliferation, suggesting that Npnt directs pNC migration into the cornea. In vitro analyses showed that Npnt promotes pNC migration from explanted periocular mesenchyme, which requires Itga8, focal adhesion kinase (FAK) and Rho kinase (ROCK). Combined, these data suggest that Npnt augments cell migration into the presumptive cornea ECM by functioning as a substrate for Itgα8-positive pNC cells.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 2-7.
Article and author information
Author details
Funding
National Eye Institute (EY031381)
- Peter Lwigale
National Eye Institute (EY022158)
- Peter Lwigale
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was conducted in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Fertilized chick embryos incubated between 1 to 17 days were handled according to the approved institutional animal care and use committee (IACUC) protocol (#IACUC-20-190) of Rice University.
Copyright
© 2022, Ma et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Nephronectin-Integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal development
eLife 11:e74307.
https://doi.org/10.7554/eLife.74307
