Region-specific roles of stress-activated protein kinase MKK7 in the developing and maturing murine brain.

The stress-responsive kinase MKK7 controls various brain functions. Previously, we showed that neural stem cell-specific deletion of the Mkk7 gene caused abnormal brain development and death immediately after birth (perinatal lethality). However, the region-specific roles of MKK7 during embryonic brain development remain unclear. In this study, we generated three strains of conditional Mkk7 knockout (Mkk7 cKO) mice with deletion of Mkk7 specifically in either the spinal cord, or midbrain/cerebellum, or cerebrum. Loss of MKK7 in the the spinal cord had no effect on mouse embryonic viability, but mice lacking MKK7 in the midbrain/cerebellum displayed perinatal lethality. In contrast, mice with loss of MKK7 in the cerebrum were born at the expected Mendelian ratio but died within five weeks of birth. The brains of these latter mutants showed a thinner cerebral cortex, enlarged ventricles, and decreased phosphorylation of microtubule-associated protein 1B (MAP1B) compared to wild type (WT) brains. This work expands our knowledge of MKK7 functions in the brain and shows that this kinase regulates brain development and maturation in a region-specific manner.