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The Hedgehog (Hh) signaling pathway regulates optic fissure development: loss\u2010of\u2010function mutations in the Hh receptor\n                      <jats:italic>ptch2<\/jats:italic>\n                      produce overactive Hh signaling and can result in coloboma. We previously proposed a model where overactive Hh signaling disrupts optic fissure formation by upregulating transcriptional targets acting both cell\u2010 and non\u2010cell\u2010autonomously. Here, we examine the Netrin family of secreted ligands as candidate Hh target genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We find multiple Netrin ligands upregulated in the zebrafish\n                      <jats:italic>ptch2<\/jats:italic>\n                      mutant during optic fissure development. Using a gain\u2010of\u2010function approach to overexpress Netrin in a spatiotemporally specific manner, we find that\n                      <jats:italic>netrin1a<\/jats:italic>\n                      or\n                      <jats:italic>netrin1b<\/jats:italic>\n                      overexpression is sufficient to cause coloboma and disrupt wild\u2010type optic fissure formation. We used loss\u2010of\u2010function alleles, CRISPR\/Cas9 mutagenesis, and morpholino knockdown to test if loss of Netrin can rescue coloboma in the\n                      <jats:italic>ptch2<\/jats:italic>\n                      mutant: loss of\n                      <jats:italic>netrin<\/jats:italic>\n                      genes does not rescue the\n                      <jats:italic>ptch2<\/jats:italic>\n                      mutant phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These results suggest that Netrin is sufficient but not required to disrupt optic fissure formation downstream of overactive Hh signaling in the\n                      <jats:italic>ptch2<\/jats:italic>\n                      mutant.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dvdy.733","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T22:22:53Z","timestamp":1724278973000},"page":"158-173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Increased Netrin downstream of overactive Hedgehog signaling disrupts optic fissure formation"],"prefix":"10.1002","volume":"254","author":[{"given":"Sarah","family":"Lusk","sequence":"first","affiliation":[{"name":"Department of Human Genetics University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"LaPotin","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason S.","family":"Presnell","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0052-275X","authenticated-orcid":false,"given":"Kristen M.","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Utah  Salt Lake City Utah 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