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Planar cell polarity genes and neurulation

The planar cell polarity (PCP) pathway is a non-canonical Wnt signalling cascade that plays a key role in vertebrate embryonic morphogenesis. 

We provided the first evidence for a link between PCP and neurulation in mammals.

IN PREVIOUS WORK, THE NEURAL TUBE GROUP HAS:

  • Identified Vangl2 as the gene mutated in the loop-tail (Lp) mouse (Murdoch et al, 2001).  Homozygotes for this mutation develop the most severe form of neural tube defect (NTD), craniorachischisis, in which the neural tube remains open from midbrain to low spine.
  • Showed that Scribble (Scrib), a gene previously known to function in apico-basal cell polarity, and Celsr1, a gene encoding a large protocadherin, are both causes of craniorachischisis in mice (Murdoch et al, 2003; Curtin et al, 2003). This identified Scribble and Celsr1 as components of the mammalian PCP pathway.
  • Demonstrated diminished convergent extension in embryos lacking Vangl2 function, as evidence that loss of PCP signalling leads to severe neural tube defects via faulty cell movements in the mouse embryo (Ybot-Gonzalez et al, 2007).
  • Identified functional mutations of the CELSR1 and SCRIB genes in humans with the severe neural tube defect, craniorachischisis (Robinson et al, 2012).

  • Demonstrated that gene-gene interaction in the PCP pathway generate diverse NTD types, providing a possible mechanism for the range of PCP-related NTDs identified in humans (Murdoch et al, 2014).
  • Discovered that neural crest specification and migration in mouse embryos proceeds normally in the absence of PCP signalling, in contrast to findings with lower vertebrates (Pryor et al, 2014).

CURRENT WORK INCLUDES:

Interactions between PCP and Grhl gene signalling in the generation of severe mouse spina bifida


PCP gene interactions with the extracellular matrix in regulating the onset of neural tube closure


Role of PCP signalling in orientation of cell division during neurulation