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First published online 29 March 2006
doi: 10.1242/dev.02347
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1 Department of Pediatrics and Medicine, University of California, San Diego,
9500 Gilman Drive, MC 0627, La Jolla, CA 92093-0627, USA.
2 Department of Cell Biology and Otolaryngology, School of Medicine, Emory
University, 615 Michael Street, Atlanta, GA 30322, USA.
3 Divison of Biology and Beckman Institute, California Institute of Technology,
Pasadena, CA 91125, USA.
4 Department of Neuroscience, University of California, San Diego, 9500 Gilman
Drive, MC 0627, La Jolla, CA 92093-0627, USA.
5 Department of Cell and Molecular Biology, House Ear Institute, 2100 West Third
Street, Los Angeles, CA 90057.
6 Molecular Cell and Developmental Biology & Institute for Cellular and
Molecular Biology, 1 University Station C0930, University of Texas, Austin, TX
78712, USA.
Author for correspondence (e-mail:
awynshawboris{at}ucsd.edu)
Accepted 7 March 2006
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.
Key words: Mouse, Planar cell polarity, Convergent extension, Neurulation
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