{"title":"Zebrafish Model of Stickler Syndrome Suggests a Role for Col2a1a in the Neural Crest during Early Eye Development.","authors":"Antionette L Williams, Brenda L Bohnsack","doi":"10.3390/jdb10040042","DOIUrl":null,"url":null,"abstract":"<p><p>Most cases of Stickler syndrome are due to autosomal-dominant COL2A1 gene mutations leading to abnormal type II collagen. Ocular findings include axial eye lengthening with vitreal degeneration and early-onset glaucoma, which can result in vision loss. Although COL2A1 is a major player in cartilage and bone formation, its specific role in eye development remains elusive. We investigated the role of Col2a1a in neural crest migration and differentiation during early zebrafish eye development. In situ hybridization, immunofluorescence, live imaging, exogenous treatments [10 μM diethylaminobenzaldehyde (DEAB), 100 nM all-trans retinoic acid (RA) and 1-3% ethanol (ETOH)] and morpholino oligonucleotide (MO) injections were used to analyze wildtype Casper (<i>roy-/-;nacre-/-</i>), TgBAC(<i>col2a1a</i>::EGFP), Tg(<i>sox10</i>::EGFP) and Tg(<i>foxd3::EGFP</i>) embryos. Col2a1a colocalized with Foxd3- and Sox10-positive cells in the anterior segment and neural crest-derived jaw. Col2a1a expression was regulated by RA and inhibited by 3% ETOH. Furthermore, MO knockdown of Col2a1a delayed jaw formation and disrupted the ocular anterior segment neural crest migration of Sox10-positive cells. Interestingly, human COL2A1 protein rescued the MO effects. Altogether, these results suggest that Col2a1a is a downstream target of RA in the cranial neural crest and is required for both craniofacial and eye development.</p>","PeriodicalId":15563,"journal":{"name":"Journal of Developmental Biology","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589970/pdf/","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Developmental Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/jdb10040042","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
引用次数: 4
Abstract
Most cases of Stickler syndrome are due to autosomal-dominant COL2A1 gene mutations leading to abnormal type II collagen. Ocular findings include axial eye lengthening with vitreal degeneration and early-onset glaucoma, which can result in vision loss. Although COL2A1 is a major player in cartilage and bone formation, its specific role in eye development remains elusive. We investigated the role of Col2a1a in neural crest migration and differentiation during early zebrafish eye development. In situ hybridization, immunofluorescence, live imaging, exogenous treatments [10 μM diethylaminobenzaldehyde (DEAB), 100 nM all-trans retinoic acid (RA) and 1-3% ethanol (ETOH)] and morpholino oligonucleotide (MO) injections were used to analyze wildtype Casper (roy-/-;nacre-/-), TgBAC(col2a1a::EGFP), Tg(sox10::EGFP) and Tg(foxd3::EGFP) embryos. Col2a1a colocalized with Foxd3- and Sox10-positive cells in the anterior segment and neural crest-derived jaw. Col2a1a expression was regulated by RA and inhibited by 3% ETOH. Furthermore, MO knockdown of Col2a1a delayed jaw formation and disrupted the ocular anterior segment neural crest migration of Sox10-positive cells. Interestingly, human COL2A1 protein rescued the MO effects. Altogether, these results suggest that Col2a1a is a downstream target of RA in the cranial neural crest and is required for both craniofacial and eye development.
期刊介绍:
The Journal of Developmental Biology (ISSN 2221-3759) is an international, peer-reviewed, quick-refereeing, open access journal, which publishes reviews, research papers and communications on the development of multicellular organisms at the molecule, cell, tissue, organ and whole organism levels. Our aim is to encourage researchers to effortlessly publish their new findings or concepts rapidly in an open access medium, overseen by their peers. There is no restriction on the length of the papers; the full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material. Journal of Developmental Biology focuses on: -Development mechanisms and genetics -Cell differentiation -Embryonal development -Tissue/organism growth -Metamorphosis and regeneration of the organisms. It involves many biological fields, such as Molecular biology, Genetics, Physiology, Cell biology, Anatomy, Embryology, Cancer research, Neurobiology, Immunology, Ecology, Evolutionary biology.