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Fat-Dachsous Signaling Coordinates Cartilage Differentiation and Polarity during Craniofacial Development


Little is known about the mechanisms of cell-cell communication necessary to assemble skeletal elements of appropriate size and shape. In this study, we investigate the roles of genetic factors belonging to a developmental pathway that affects skeletal progenitor behavior: the atypical cadherins Fat3 and Dachsous2 (Dchs2), and REREa/Atr2a. We show that cartilage precursors fail to rearrange into linear stacks and at the same time misregulate expression of sox9a, a key regulator of cartilage differentiation, in zebrafish embryos deficient in Fat3 or its partner Dchs2. Similar cartilage defects are observed in rerea−/− mutants, and Fat3 interacts physically and genetically with REREa. Our results suggest that Fat3, Dchs2 and REREa interact to control polarized cell-cell intercalation and simultaneously control skeletal differentiation through Sox9. By transplanting cartilage precursors between wild-type and Fat3, Dchs2 or REREa deficient embryos we demonstrate that all three factors exert long-range influences on neighboring cells, most likely mediated by another polarizing signal. We propose a model in which this coordinates the polarity and differentiation of chondrocytes to shape skeletal primordia, and that defects in these processes underlie human skeletal malformations.


Vyšlo v časopise: Fat-Dachsous Signaling Coordinates Cartilage Differentiation and Polarity during Craniofacial Development. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004726
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004726

Souhrn

Little is known about the mechanisms of cell-cell communication necessary to assemble skeletal elements of appropriate size and shape. In this study, we investigate the roles of genetic factors belonging to a developmental pathway that affects skeletal progenitor behavior: the atypical cadherins Fat3 and Dachsous2 (Dchs2), and REREa/Atr2a. We show that cartilage precursors fail to rearrange into linear stacks and at the same time misregulate expression of sox9a, a key regulator of cartilage differentiation, in zebrafish embryos deficient in Fat3 or its partner Dchs2. Similar cartilage defects are observed in rerea−/− mutants, and Fat3 interacts physically and genetically with REREa. Our results suggest that Fat3, Dchs2 and REREa interact to control polarized cell-cell intercalation and simultaneously control skeletal differentiation through Sox9. By transplanting cartilage precursors between wild-type and Fat3, Dchs2 or REREa deficient embryos we demonstrate that all three factors exert long-range influences on neighboring cells, most likely mediated by another polarizing signal. We propose a model in which this coordinates the polarity and differentiation of chondrocytes to shape skeletal primordia, and that defects in these processes underlie human skeletal malformations.


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Genetika Reprodukčná medicína

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