An expanding role of Vangl proteins in embryonic development

Abstract

The mammalian Vangl1 and Vangl2 genes were discovered a decade ago through their association with neural tube defects, in particular the presence of Vangl2 mutations in independent alleles of the mouse mutant Loop-tail (Lp), a mouse model of the severe neural tube defect craniorachischisis. Vangl1 and Vangl2 variants have also been detected in familial and sporadic cases of spina bifida. Vangl proteins are highly conserved in evolution with relatives in flies, and distant invertebrates and vertebrates. In these organisms, they play a central role in planar cell polarity (PCP) and convergent extension (CE) movements. Over the past decade, these functional characteristics have also been established for mammalian Vangl genes. The careful analysis of mouse Vangl genes mutants has showed that these genes and the associated PCP pathway and CE movements are involved in many unexpected developmental processes, from morphogenesis of different tissues, left-right asymmetry, asymmetric cell division, and organization of many epithelial structures, as well as positioning and function of cellular appendages. Genetic studies in double mutants and biochemical studies of interacting proteins have started to elucidate the molecular pathways in which Vangl proteins participate and that regulate these complex events.