Disruption of the foxe1 gene in zebrafish reveals conserved functions in development of the craniofacial skeleton and the thyroid.

Autor:	Raterman ST; Department of Dentistry-Orthodontics and Craniofacial Biology, Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands.; Department of Animal Ecology and Physiology, Radboud Institute for Biological and Environmental Sciences (RIBES), Radboud University, Nijmegen, Netherlands., Von Den Hoff JW; Department of Dentistry-Orthodontics and Craniofacial Biology, Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands., Dijkstra S; Department of Animal Ecology and Physiology, Radboud Institute for Biological and Environmental Sciences (RIBES), Radboud University, Nijmegen, Netherlands., De Vriend C; Department of Animal Ecology and Physiology, Radboud Institute for Biological and Environmental Sciences (RIBES), Radboud University, Nijmegen, Netherlands., Te Morsche T; Department of Animal Ecology and Physiology, Radboud Institute for Biological and Environmental Sciences (RIBES), Radboud University, Nijmegen, Netherlands., Broekman S; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Zethof J; Department of Animal Ecology and Physiology, Radboud Institute for Biological and Environmental Sciences (RIBES), Radboud University, Nijmegen, Netherlands., De Vrieze E; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Wagener FADTG; Department of Dentistry-Orthodontics and Craniofacial Biology, Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands., Metz JR; Department of Animal Ecology and Physiology, Radboud Institute for Biological and Environmental Sciences (RIBES), Radboud University, Nijmegen, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2023 Mar 13; Vol. 11, pp. 1143844. Date of Electronic Publication: 2023 Mar 13 (Print Publication: 2023).
DOI:	10.3389/fcell.2023.1143844
Abstrakt:	Introduction: Mutations in the FOXE1 gene are implicated in cleft palate and thyroid dysgenesis in humans. Methods: To investigate whether zebrafish could provide meaningful insights into the etiology of developmental defects in humans related to FOXE1, we generated a zebrafish mutant that has a disruption in the nuclear localization signal in the foxe1 gene, thereby restraining nuclear access of the transcription factor. We characterized skeletal development and thyroidogenesis in these mutants, focusing on embryonic and larval stages. Results: Mutant larvae showed aberrant skeletal phenotypes in the ceratohyal cartilage and had reduced whole body levels of Ca, Mg and P, indicating a critical role for foxe1 in early skeletal development. Markers of bone and cartilage (precursor) cells were differentially expressed in mutants in post-migratory cranial neural crest cells in the pharyngeal arch at 1 dpf, at induction of chondrogenesis at 3 dpf and at the start of endochondral bone formation at 6 dpf. Foxe1 protein was detected in differentiated thyroid follicles, suggesting a role for the transcription factor in thyroidogenesis, but thyroid follicle morphology or differentiation were unaffected in mutants. Discussion: Taken together, our findings highlight the conserved role of Foxe1 in skeletal development and thyroidogenesis, and show differential signaling of osteogenic and chondrogenic genes related to foxe1 mutation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Raterman, Von Den Hoff, Dijkstra, De Vriend, Te Morsche, Broekman, Zethof, De Vrieze, Wagener and Metz.)
Databáze:	MEDLINE
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