Nephronectin-integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal development
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 regi...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/74307 |
| _version_ | 1811200500494761984 |
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| author | Justin Ma Lian Bi James Spurlin Peter Lwigale |
| author_facet | Justin Ma Lian Bi James Spurlin Peter Lwigale |
| author_sort | Justin Ma |
| collection | DOAJ |
| description | 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 (Itgα8) receptor. Knockdown of either Npnt or Itgα8 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 nor 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 Itgα8, focal adhesion kinase, and Rho kinase. Combined, these data suggest that Npnt augments cell migration into the presumptive cornea extracellular matrix by functioning as a substrate for Itgα8-positive pNC cells. |
| first_indexed | 2024-04-12T02:05:14Z |
| format | Article |
| id | doaj.art-fc03e27442ff48288377fdc92dd52b38 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:05:14Z |
| publishDate | 2022-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-fc03e27442ff48288377fdc92dd52b382022-12-22T03:52:34ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.74307Nephronectin-integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal developmentJustin Ma0Lian Bi1James Spurlin2Peter Lwigale3https://orcid.org/0000-0003-1799-4905Department of Biosciences, Rice University, Houston, United StatesDepartment of Biosciences, Rice University, Houston, United StatesDepartment of Biosciences, Rice University, Houston, United StatesDepartment of Biosciences, Rice University, Houston, United StatesDuring 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 (Itgα8) receptor. Knockdown of either Npnt or Itgα8 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 nor 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 Itgα8, focal adhesion kinase, and Rho kinase. Combined, these data suggest that Npnt augments cell migration into the presumptive cornea extracellular matrix by functioning as a substrate for Itgα8-positive pNC cells.https://elifesciences.org/articles/74307periocular neural crestextracellular matrixcorneal developmentnephronectinintegrin alpha 8cornea |
| spellingShingle | Justin Ma Lian Bi James Spurlin Peter Lwigale Nephronectin-integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal development eLife periocular neural crest extracellular matrix corneal development nephronectin integrin alpha 8 cornea |
| title | Nephronectin-integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal development |
| title_full | Nephronectin-integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal development |
| title_fullStr | Nephronectin-integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal development |
| title_full_unstemmed | Nephronectin-integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal development |
| title_short | Nephronectin-integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal development |
| title_sort | nephronectin integrin α8 signaling is required for proper migration of periocular neural crest cells during chick corneal development |
| topic | periocular neural crest extracellular matrix corneal development nephronectin integrin alpha 8 cornea |
| url | https://elifesciences.org/articles/74307 |
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