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Author Notes:

Anthony Wynshaw - Boris: awynshawboris@ucsd.edu.

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).

Subjects:

Research Funding:

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.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Developmental Biology
  • mouse
  • planar cell polarity
  • convergent extension
  • neurulation
  • PLANAR CELL-POLARITY
  • NEURAL-TUBE CLOSURE
  • SUBCELLULAR-LOCALIZATION
  • TISSUE POLARITY
  • LOOP-TAIL
  • GASTRULATION MOVEMENTS
  • STRABISMUS/VAN-GOGH
  • EARLY EMBRYOGENESIS
  • VERTEBRATE EMBRYOS
  • SIGNALING PATHWAYS

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

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Journal Title:

Development

Volume:

Volume 133, Number 9

Publisher:

, Pages 1767-1778

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

Copyright information:

© 2006. THE COMPANY OF BIOLOGISTS LTD.

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