The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development

The c-Jun NH2-terminal kinase (Jnk) family is implicated in apoptosis, but its function in brain development is unclear. Here, we address this issue u sing mutant mice lacking different members of the family (Jnk1, Jnk2, and J nk3). Mice deficient in Jnk1, Jnk2, Jnk3, and Jnk1/Jnk3 or Jnk2/Jnk3 double mutants all survived normally. Compound mutants lacking Jnk1 and Jnk2 gene s were embryonic lethal and had severe dysregulation of apoptosis in brain. Specifically, there was a reduction of cell death in the lateral edges of hindbrain prior to neural tube closure. In contrast, increased apoptosis an d caspase activation were found in the mutant forebrain, leading to precoci ous degeneration. These results suggest that Jnk1 and Jnk2 regulate region- specific apoptosis during early brain development.