A combination of neural tube defects, open eyelids, and inner ear defects suggests a role for Cecr2 in regulation of the planar cell polarity pathway

The chromatin remodeling protein CECR2 is required for development of the neural tube in mice and loss of Cecr2 results in the cranial neural tube defect exencephaly and open eyelids. In mice homozygous for a Cecr2 mutation, I have shown that the neural folds elevate but fail to approach. X-gal staining revealed strong Cecr2 expression in the neural epithelium during neurulation. Examination of the inner ear morphology of 18.5dpc embryos showed significant misalignment of the stereocilia in the Cecr2m/m, and to a lesser degree in the Cecr2+/m, suggesting dosage sensitivity. X-gal staining confirmed Cecr2 expression in the cochlea. Neural tube defects, open eyelids, and stereocilia misalignment are the three hallmarks of planar cell polarity (PCP) pathway defects. Cecr2m/m non-penetrant for the exencephaly also shows sub-fertility like other PCP mutants. The connection of Cecr2 to the PCP pathway indicates that Cecr2 may regulate genes in this critical developmental pathway.