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Background  The planar cell polarity (PCP) signalling pathway is fundamental to a number of key developmental events, including initiation of neural tube closure. Disruption of the PCP pathway causes the severe neural tube defect of craniorachischisis, in which almost the entire brain and spinal cord fails to close. Identification of mouse mutants with craniorachischisis has proven a powerful way of identifying molecules that are components or regulators of the PCP pathway. In addition, identification of an allelic series of mutants, including hypomorphs and neomorphs in addition to complete nulls, can provide novel genetic tools to help elucidate the function of the PCP proteins.    Results  We report the identification of a new N-ethyl-N-nitrosourea (ENU)-induced mutant with craniorachischisis, which we have named  chuzhoi  ( chz ). We demonstrate that  chuzhoi  mutant embryos fail to undergo initiation of neural tube closure, and have characteristics consistent with defective convergent extension. These characteristics include a broadened midline and reduced rate of increase of their length-to-width ratio. In addition, we demonstrate disruption in the orientation of outer hair cells in the inner ear, and defects in heart and lung development in  chuzhoi  mutants. We demonstrate a genetic interaction between  chuzhoi  mutants and both  Vangl2   Lp   and  Celsr1   Crsh   mutants, strengthening the hypothesis that  chuzhoi  is involved in regulating the PCP pathway. We demonstrate that  chuzhoi  maps to Chromosome 17 and carries a splice site mutation in  Ptk7 . This mutation results in the insertion of three amino acids into the Ptk7 protein and causes disruption of Ptk7 protein expression in  chuzhoi  mutants.    Conclusions  The  chuzhoi  mutant provides an additional genetic resource to help investigate the developmental basis of several congenital abnormalities including neural tube, heart and lung defects and their relationship to disruption of PCP. The  chuzhoi  mutation differentially affects the expression levels of the two Ptk7 protein isoforms and, while some Ptk7 protein can still be detected at the membrane,  chuzhoi  mutants demonstrate a significant reduction in membrane localization of Ptk7 protein. This mutant provides a useful tool to allow future studies aimed at understanding the molecular function of Ptk7.

bmc developmental biology

The novel mouse mutant, chuzhoi, has disruption of Ptk7 protein and exhibits defects in neural tube, heart and lung development and abnormal planar cell polarity in the ear