The Jnk1 and Jnk2 Protein Kinases Are Required for Regional Specific Apoptosis During Early Brain Development

Neuron. 1999 Apr;22(4):667-76. doi: 10.1016/s0896-6273(00)80727-8.

Abstract

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 using mutant mice lacking different members of the family (Jnk1, Jnk2, and Jnk3). Mice deficient in Jnk1, Jnk2, Jnk3, and Jnk1/Jnk3 or Jnk2/Jnk3 double mutants all survived normally. Compound mutants lacking Jnk1 and Jnk2 genes 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 and caspase activation were found in the mutant forebrain, leading to precocious degeneration. These results suggest that Jnk1 and Jnk2 regulate region-specific apoptosis during early brain development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Brain / embryology
  • Brain / metabolism*
  • Brain / pathology
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Caspases / metabolism
  • Embryonic and Fetal Development / physiology
  • Enzyme Activation
  • Gene Expression Regulation, Developmental / physiology
  • Gene Expression Regulation, Enzymologic / physiology
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases*
  • Nervous System / embryology
  • Nervous System / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Rhombencephalon / embryology
  • Rhombencephalon / metabolism

Substances

  • Protein Kinases
  • Mitogen-Activated Protein Kinase 9
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Caspases