Querkopf, a MYST family histone acetyltransferase, is required for normal cerebral cortex development

In order to find, and mutate, novel genes required for regulation of neurogenesis in the cerebral cortex, we performed a genetic screen in mice. As the result of this screen, we created a new mouse mutant, querkopf. The querkopf mutation is due to an insertion into a MYST family histone acetyltransferase gene. Mice homozygous for the querkopf mutation have craniofacial abnormalities, fail to thrive in the postnatal period and have defects in central nervous system development. The defects in central nervous system development are particularly prominent in the cerebral cortex, which is disproportionally smaller than in wild-type mice. A large reduction in the size of the cortical plate was already apparent during embryogenesis. Homozygous mice show a lack of large pyramidal cells in layer V of the cortex, which is reflected in a reduction in the number of Otx1-positive neurons in this layer during postnatal development. Homozygous mice also show a reduction in the number of GAD67-positive interneurons throughout the cortex. Our results suggest that Querkopf is an essential component of a genetic cascade regulating cell differentiation in the cortex, probably acting in a multiprotein complex regulating chromatin structure during transcription.