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

Mice lacking both c-Jun-NH2-terminal kinases (JNK1 and JNK2) were generated to define their roles in development. Jnk1/jnk2 double mutant fetuses die around embryonic day 11 (E11) and were found to display an open neural tube (exencephaly) at the hindbrain level with reduced apaptosis in the hindbra in neuroepithelium at E9.25. In contrast, a dramatic increase in cell death was observed one day later at E10.5 in both the hindbrain and forebrain re gions. Moreover, about 25% of jnk1 -/- jnk2 +/- fetuses display exencephaly probably due to reduced levels of JNK proteins, whereas jnk1 +/- jnk2 +/- mice are viable. These results assign both pro- and anti-apoptotic function s to JNK1 and JNK2 in the development of the fetal brain. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.