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Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation

Wang, Jianbo and Hamblet, Natasha S. and Mark, Sharayne and Dickinson, Mary E. and Brinkman, Brendan C. and Segil, Neil and Fraser, Scott E. and Chen, Ping and Wallingford, John B. and Wynshaw-Boris, Anthony (2006) Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation. Development, 133 (9). pp. 1767-1778. ISSN 0950-1991. PMCID PMC4158842.

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The planar cell polarity (PCP) pathway is conserved throughout evolution, but it mediates distinct developmental processes. In Drosophila, members of the PCP pathway localize in a polarized fashion to specify the cellular polarity within the plane of the epithelium, perpendicular to the apicobasal axis of the cell. In Xenopus and zebrafish, several homologs of the components of the fly PCP pathway control convergent extension. We have shown previously that mammalian PCP homologs regulate both cell polarity and polarized extension in the cochlea in the mouse. Here we show, using mice with null mutations in two mammalian Dishevelled homologs, Dvl1 and Dvl2, that during neurulation a homologous mammalian PCP pathway regulates concomitant lengthening and narrowing of the neural plate, a morphogenetic process defined as convergent extension. Dvl2 genetically interacts with Loop-tail, a point mutation in the mammalian PCP gene Vangl2, during neurulation. By generating Dvl2 BAC (bacterial artificial chromosome) transgenes and introducing different domain deletions and a point mutation identical to the dsh1 allele in fly, we further demonstrated a high degree of conservation between Dvl function in mammalian convergent extension and the PCP pathway in fly. In the neuroepithelium of neurulating embryos, Dvl2 shows DEP domain-dependent membrane localization, a pre-requisite for its involvement in convergent extension. Intriguing, the Loop-tail mutation that disrupts both convergent extension in the neuroepithelium and PCP in the cochlea does not disrupt Dvl2 membrane distribution in the neuroepithelium, in contrast to its drastic effect on Dvl2 localization in the cochlea. These results are discussed in light of recent models on PCP and convergent extension.

Item Type:Article
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URLURL TypeDescription CentralArticle
Fraser, Scott E.0000-0002-5377-0223
Additional Information:© The Company of Biologists Ltd 2006. Accepted 7 March 2006. First published online 29 March 2006. We thank Ella Kothari and Jun Zhao in the UCSD Cancer Center Transgenic Core for transgenic service, and the UCSD/NINDS Neuroscience Core (NINDS P30 NS047101). This work is supported by a Pete Lopiccola Fellowship, a Clifford and Evelyn Cherry Fellowship and an AHA postdoctoral fellowship to J.W.; a Burroughs Wellcome Fund Career Award in the Biomedical Sciences to J.B.W.; and by grants from the National Institute of Health to J.B.W. (R01 GM074104), A.W.B. (R01 HD43173-02) and P.C. (R01 DC005213); and the Woodruff Foundation to P.C.
Funding AgencyGrant Number
NIHP30 NS047101
University of California San DiegoUNSPECIFIED
American Heart AssociationUNSPECIFIED
Burroughs Wellcome FundUNSPECIFIED
NIHR01 GM074104
NIHR01 HD43173-02
NIHR01 DC005213
Robert W. Woodruff FoundationUNSPECIFIED
National Institute of Neurological Disorders and Stroke (NINDS)UNSPECIFIED
Subject Keywords:Mouse; Planar cell polarity; Convergent extension; Neurulation
Issue or Number:9
PubMed Central ID:PMC4158842
Record Number:CaltechAUTHORS:20090917-152415327
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Official Citation:Jianbo Wang, Natasha S. Hamblet, Sharayne Mark, Mary E. Dickinson, Brendan C. Brinkman, Neil Segil, Scott E. Fraser, Ping Chen, John B. Wallingford, and Anthony Wynshaw-Boris Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation First published online on 1 May 2006 Development 133, 10.1242/dev.02347 (2006)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15932
Deposited By: George Porter
Deposited On:22 Sep 2009 18:45
Last Modified:03 Oct 2019 01:05

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