{"title":"Lineage-specific requirements of Alx4 function in craniofacial and hair development","authors":"Yu Lan, Zhaoming Wu, Han Liu, Rulang Jiang","doi":"10.1002/dvdy.705","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Disruption of <i>ALX4</i> causes autosomal dominant parietal foramina and autosomal recessive frontonasal dysplasia with alopecia, but the mechanisms involving ALX4 in craniofacial and other developmental processes are not well understood. Although mice carrying distinct mutations in <i>Alx4</i> have been previously reported, the perinatal lethality of homozygous mutants together with dynamic patterns of <i>Alx4</i> expression in multiple tissues have hindered systematic elucidation of the cellular and molecular mechanisms involving Alx4 in organogenesis and disease pathogenesis.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We report generation of <i>Alx4</i><sup><i>f/f</i></sup> conditional mice and show that tissue-specific Cre-mediated inactivation of <i>Alx4</i> in cranial neural crest and limb bud mesenchyme, respectively, recapitulated craniofacial and limb developmental defects as found in <i>Alx4</i>-null mice but without affecting postnatal survival. While <i>Alx4</i>-null mice that survive postnatally exhibited dorsal alopecia, mice lacking <i>Alx4</i> function in the neural crest lineage exhibited a highly restricted region of hair loss over the anterior skull whereas mice lacking <i>Alx4</i> in the cranial mesoderm lineage exhibited normal hair development, suggesting that Alx4 plays partly redundant roles in multiple cell lineages during hair follicle development.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>The <i>Alx4</i><sup><i>f/f</i></sup> mice provide a valuable resource for systematic investigation of cell type- and stage-specific function of ALX family transcription factors in development and disease.</p>\n </section>\n </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 10","pages":"940-948"},"PeriodicalIF":2.0000,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental Dynamics","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/dvdy.705","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Disruption of ALX4 causes autosomal dominant parietal foramina and autosomal recessive frontonasal dysplasia with alopecia, but the mechanisms involving ALX4 in craniofacial and other developmental processes are not well understood. Although mice carrying distinct mutations in Alx4 have been previously reported, the perinatal lethality of homozygous mutants together with dynamic patterns of Alx4 expression in multiple tissues have hindered systematic elucidation of the cellular and molecular mechanisms involving Alx4 in organogenesis and disease pathogenesis.
Results
We report generation of Alx4f/f conditional mice and show that tissue-specific Cre-mediated inactivation of Alx4 in cranial neural crest and limb bud mesenchyme, respectively, recapitulated craniofacial and limb developmental defects as found in Alx4-null mice but without affecting postnatal survival. While Alx4-null mice that survive postnatally exhibited dorsal alopecia, mice lacking Alx4 function in the neural crest lineage exhibited a highly restricted region of hair loss over the anterior skull whereas mice lacking Alx4 in the cranial mesoderm lineage exhibited normal hair development, suggesting that Alx4 plays partly redundant roles in multiple cell lineages during hair follicle development.
Conclusion
The Alx4f/f mice provide a valuable resource for systematic investigation of cell type- and stage-specific function of ALX family transcription factors in development and disease.
期刊介绍:
Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.