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ZFIN ID: ZDB-PUB-170608-5
The signalling receptor MCAM coordinates apical-basal polarity and planar cell polarity during morphogenesis
Gao, Q., Zhang, J., Wang, X., Liu, Y., He, R., Liu, X., Wang, F., Feng, J., Yang, D., Wang, Z., Meng, A., Yan, X.
Date: 2017
Source: Nature communications   8: 15279 (Journal)
Registered Authors: Liu, Ying, Meng, Anming, Zhang, Junfeng
Keywords: Body patterning, Cell polarity
MeSH Terms:
  • Animals
  • Body Patterning
  • CD146 Antigen/metabolism*
  • Cell Polarity*
  • Cilia/metabolism
  • Enzyme Activation
  • Fibroblast Growth Factor 4/metabolism
  • Gene Deletion
  • HEK293 Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases/metabolism
  • Morphogenesis*
  • NFATC Transcription Factors/metabolism
  • Phospholipase C gamma/metabolism
  • Protein Transport
  • Signal Transduction*
  • Transport Vesicles/metabolism
  • Xenopus
  • Xenopus Proteins/metabolism*
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism*
PubMed: 28589943 Full text @ Nat. Commun.
The apical-basal (AB) polarity and planar cell polarity (PCP) provide an animal cell population with different phenotypes during morphogenesis. However, how cells couple these two patterning systems remains unclear. Here we provide in vivo evidence that melanoma cell adhesion molecule (MCAM) coordinates AB polarity-driven lumenogenesis and c-Jun N-terminal kinase (JNK)/PCP-dependent ciliogenesis. We identify that MCAM is an independent receptor of fibroblast growth factor 4 (FGF4), a membrane anchor of phospholipase C-γ (PLC-γ), an immediate upstream receptor of nuclear factor of activated T-cells (NFAT) and a constitutive activator of JNK. We find that MCAM-mediated vesicular trafficking towards FGF4, while generating a priority-grade transcriptional response of NFAT determines lumenogenesis. We demonstrate that MCAM plays indispensable roles in ciliogenesis through activating JNK independently of FGF signals. Furthermore, mcam-deficient zebrafish and Xenopus exhibit a global defect in left-right (LR) asymmetric establishment as a result of morphogenetic failure of their LR organizers. Therefore, MCAM coordination of AB polarity and PCP provides insight into the general mechanisms of morphogenesis.