Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2

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K Sabapathy1, W Jochum, K Hochedlinger

  • 1Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030, Vienna, Austria.

Mechanisms of Development
|November 24, 1999
PubMed

Insights

Mice lacking c-Jun-NH(2)-terminal kinases (JNK1 and JNK2) show developmental defects, including an open neural tube. JNK1 and JNK2 have dual roles in fetal brain development, acting as both pro- and anti-apoptotic factors.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Neuroscience

Background:

  • c-Jun-NH(2)-terminal kinases (JNK1 and JNK2) are crucial signaling molecules.
  • Their precise roles in embryonic development, particularly in the central nervous system, remain incompletely understood.

Purpose of the Study:

  • To investigate the function of JNK1 and JNK2 during embryonic development.
  • To elucidate the roles of JNK1 and JNK2 in fetal brain formation and cell death processes.

Main Methods:

  • Generation of Jnk1/Jnk2 double knockout mice.
  • Analysis of embryonic phenotypes, including neural tube closure and apoptosis.
  • Assessment of JNK protein levels in mutant embryos.

Main Results:

  • Jnk1/Jnk2 double mutant fetuses exhibit embryonic lethality around E11.
  • Exencephaly (open neural tube) was observed in double mutants, associated with altered apoptosis in the hindbrain.
  • A shift in apoptotic activity was noted, with reduced cell death early (E9.25) and increased cell death later (E10.5) in the hindbrain and forebrain.
  • Partial loss of JNK function (jnk1-/-jnk2+/-) also led to exencephaly, indicating a dose-dependent effect.

Conclusions:

  • JNK1 and JNK2 play critical, complex roles in fetal brain development.
  • These kinases exhibit both pro-apoptotic and anti-apoptotic functions depending on the developmental stage and brain region.
  • Disruption of JNK signaling pathways can lead to severe developmental abnormalities such as exencephaly.

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