Biomedical Engineering Reference
In-Depth Information
CHAPTER TEN
An Expanding Role of Vangl
Proteins in Embryonic
Development
Elena Torban
*
, Alexandra Iliescu
†
,
‡
, Philippe Gros
†
,
‡
,1
*Department of Medicine, McGill University, Montreal, Quebec, Canada
†
Department of Biochemistry, McGill University, Montreal, Quebec, Canada
‡
Complex Traits Group, McGill University, Montreal, Quebec, Canada
1
Corresponding author: e-mail address: philippe.gros@mcgill.ca
Contents
1. Vangl Proteins, Neurulation, and Neural Tube Defects
238
2. Vangl Proteins, Planar Cell Polarity, and Tissue Patterning
242
3. Role of Vangl2 in Structure and Function of Ciliated Cells
248
4. Cellular and Molecular Mechanism of Action of Vangl2 in Vertebrates
252
5. Conclusions
255
Acknowledgments
255
References
256
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 con-
served 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, frommorpho-
genesis of different tissues, left
-
right asymmetry, asymmetric cell division, and organi-
zation 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.
