Mutation of <i>foxl1</i> Results in Reduced Cartilage Markers in a Zebrafish Model of Otosclerosis
Bone diseases such as otosclerosis (conductive hearing loss) and osteoporosis (low bone mineral density) can result from the abnormal expression of genes that regulate cartilage and bone development. The forkhead box transcription factor <i>FOXL1</i> has been identified as the causative...
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MDPI AG
2022-06-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/7/1107 |
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| author | Alexia Hawkey-Noble Justin A. Pater Roshni Kollipara Meriel Fitzgerald Alexandre S. Maekawa Christopher S. Kovacs Terry-Lynn Young Curtis R. French |
| author_facet | Alexia Hawkey-Noble Justin A. Pater Roshni Kollipara Meriel Fitzgerald Alexandre S. Maekawa Christopher S. Kovacs Terry-Lynn Young Curtis R. French |
| author_sort | Alexia Hawkey-Noble |
| collection | DOAJ |
| description | Bone diseases such as otosclerosis (conductive hearing loss) and osteoporosis (low bone mineral density) can result from the abnormal expression of genes that regulate cartilage and bone development. The forkhead box transcription factor <i>FOXL1</i> has been identified as the causative gene in a family with autosomal dominant otosclerosis and has been reported as a candidate gene in GWAS meta-analyses for osteoporosis. This potentially indicates a novel role for <i>foxl1</i> in chondrogenesis, osteogenesis, and bone remodelling. We created a <i>foxl1</i> mutant zebrafish strain as a model for otosclerosis and osteoporosis and examined jaw bones that are homologous to the mammalian middle ear bones, and mineralization of the axial skeleton. We demonstrate that <i>foxl1</i> regulates the expression of collagen genes such as <i>collagen type 1 alpha 1a</i> and <i>collagen type 11 alpha 2</i>, and results in a delay in jawbone mineralization, while the axial skeleton remains unchanged. <i>foxl1</i> may also act with other forkhead genes such as <i>foxc1a</i>, as loss of <i>foxl1</i> in a <i>foxc1a</i> mutant background increases the severity of jaw calcification phenotypes when compared to each mutant alone. Our zebrafish model demonstrates atypical cartilage formation and mineralization in the zebrafish craniofacial skeleton in <i>foxl1</i> mutants and demonstrates that aberrant collagen expression may underlie the development of otosclerosis. |
| first_indexed | 2024-03-09T11:52:55Z |
| format | Article |
| id | doaj.art-e14ba94367d24be6becbf5145c627adf |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T11:52:55Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-e14ba94367d24be6becbf5145c627adf2023-11-30T23:13:51ZengMDPI AGGenes2073-44252022-06-01137110710.3390/genes13071107Mutation of <i>foxl1</i> Results in Reduced Cartilage Markers in a Zebrafish Model of OtosclerosisAlexia Hawkey-Noble0Justin A. Pater1Roshni Kollipara2Meriel Fitzgerald3Alexandre S. Maekawa4Christopher S. Kovacs5Terry-Lynn Young6Curtis R. French7Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaBone diseases such as otosclerosis (conductive hearing loss) and osteoporosis (low bone mineral density) can result from the abnormal expression of genes that regulate cartilage and bone development. The forkhead box transcription factor <i>FOXL1</i> has been identified as the causative gene in a family with autosomal dominant otosclerosis and has been reported as a candidate gene in GWAS meta-analyses for osteoporosis. This potentially indicates a novel role for <i>foxl1</i> in chondrogenesis, osteogenesis, and bone remodelling. We created a <i>foxl1</i> mutant zebrafish strain as a model for otosclerosis and osteoporosis and examined jaw bones that are homologous to the mammalian middle ear bones, and mineralization of the axial skeleton. We demonstrate that <i>foxl1</i> regulates the expression of collagen genes such as <i>collagen type 1 alpha 1a</i> and <i>collagen type 11 alpha 2</i>, and results in a delay in jawbone mineralization, while the axial skeleton remains unchanged. <i>foxl1</i> may also act with other forkhead genes such as <i>foxc1a</i>, as loss of <i>foxl1</i> in a <i>foxc1a</i> mutant background increases the severity of jaw calcification phenotypes when compared to each mutant alone. Our zebrafish model demonstrates atypical cartilage formation and mineralization in the zebrafish craniofacial skeleton in <i>foxl1</i> mutants and demonstrates that aberrant collagen expression may underlie the development of otosclerosis.https://www.mdpi.com/2073-4425/13/7/1107<i>foxl1</i><i>foxc1</i>zebrafishotosclerosiscollagenosteoporosis |
| spellingShingle | Alexia Hawkey-Noble Justin A. Pater Roshni Kollipara Meriel Fitzgerald Alexandre S. Maekawa Christopher S. Kovacs Terry-Lynn Young Curtis R. French Mutation of <i>foxl1</i> Results in Reduced Cartilage Markers in a Zebrafish Model of Otosclerosis Genes <i>foxl1</i> <i>foxc1</i> zebrafish otosclerosis collagen osteoporosis |
| title | Mutation of <i>foxl1</i> Results in Reduced Cartilage Markers in a Zebrafish Model of Otosclerosis |
| title_full | Mutation of <i>foxl1</i> Results in Reduced Cartilage Markers in a Zebrafish Model of Otosclerosis |
| title_fullStr | Mutation of <i>foxl1</i> Results in Reduced Cartilage Markers in a Zebrafish Model of Otosclerosis |
| title_full_unstemmed | Mutation of <i>foxl1</i> Results in Reduced Cartilage Markers in a Zebrafish Model of Otosclerosis |
| title_short | Mutation of <i>foxl1</i> Results in Reduced Cartilage Markers in a Zebrafish Model of Otosclerosis |
| title_sort | mutation of i foxl1 i results in reduced cartilage markers in a zebrafish model of otosclerosis |
| topic | <i>foxl1</i> <i>foxc1</i> zebrafish otosclerosis collagen osteoporosis |
| url | https://www.mdpi.com/2073-4425/13/7/1107 |
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