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XB-ART-53738
Nat Commun January 1, 2017; 8 15279.

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 .


Abstract
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.

PubMed ID: 28589943
PMC ID: PMC5467231
Article link: Nat Commun

Genes referenced: cdc42 dnai1 fgf2 fgf4 fgf8 fgfr1 fgfr2 fyn jun lefty mapk8 mcam nfatc2 nodal1 ppp3ca prkci sox17b.1 tp53


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References [+] :
Allen, Role of heparan sulfate as a tissue-specific regulator of FGF-4 and FGF receptor recognition. 2001, Pubmed


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