Fat-Dachsous signaling coordinates cartilage differentiation and polarity during craniofacial development
| Autor: | Carrie Ng, Thomas F. Schilling, Pierre Le Pabic |
|---|---|
| Přispěvatelé: | Mullins, Mary C |
| Rok vydání: | 2014 |
| Předmět: |
Embryology
Cancer Research Cellular differentiation Cell Communication 0302 clinical medicine Cell polarity Morphogenesis Developmental Zebrafish Genetics (clinical) Pediatric 0303 health sciences Gene Expression Regulation Developmental Cell Polarity Cell Differentiation SOX9 Transcription Factor Cadherins Cell biology medicine.anatomical_structure Research Article Cell signaling lcsh:QH426-470 1.1 Normal biological development and functioning Embryonic Development Organogenesis Biology 03 medical and health sciences Chondrocytes Underpinning research medicine Genetics Animals Humans Dental/Oral and Craniofacial Disease Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Cadherin Cartilage Biology and Life Sciences Zebrafish Proteins biology.organism_classification lcsh:Genetics Gene Expression Regulation Musculoskeletal Congenital Structural Anomalies 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | PLoS genetics, vol 10, iss 10 Le Pabic, P; Ng, C; & Schilling, TF. (2014). Fat-Dachsous Signaling Coordinates Cartilage Differentiation and Polarity during Craniofacial Development. PLoS Genetics, 10(10). doi: 10.1371/journal.pgen.1004726. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/9s28c4js PLoS Genetics PLoS Genetics, Vol 10, Iss 10, p e1004726 (2014) |
| Popis: | Organogenesis requires coordinated regulation of cellular differentiation and morphogenesis. Cartilage cells in the vertebrate skeleton form polarized stacks, which drive the elongation and shaping of skeletal primordia. Here we show that an atypical cadherin, Fat3, and its partner Dachsous-2 (Dchs2), control polarized cell-cell intercalation of cartilage precursors during craniofacial development. In zebrafish embryos deficient in Fat3 or Dchs2, chondrocytes fail to stack and misregulate expression of sox9a. Similar morphogenetic defects occur in rerea/atr2a −/− mutants, and Fat3 binds REREa, consistent with a model in which Fat3, Dchs2 and REREa interact to control polarized cell-cell intercalation and simultaneously control differentiation through Sox9. Chimaeric analyses support such a model, and reveal long-range influences of all three factors, consistent with the activation of a secondary signal that regulates polarized cell-cell intercalation. This coordinates the spatial and temporal morphogenesis of chondrocytes to shape skeletal primordia and defects in these processes underlie human skeletal malformations. Similar links between cell polarity and differentiation mechanisms are also likely to control organ formation in other contexts. Author Summary 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. |
| Databáze: | OpenAIRE |
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