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J. Cell Biol.,
Volume 145, Number 5, May 31, 1999 1049-1061
* Department of Pathology, University of Graz, A-8036 Graz, Austria; Mice lacking the AP-1 transcription factor
c-Jun die around embryonic day E13.0 but little is
known about the cell types affected as well as the cause
of embryonic lethality. Here we show that a fraction of
mutant E13.0 fetal livers exhibits extensive apoptosis of
both hematopoietic cells and hepatoblasts, whereas the
expression of 15 mRNAs, including those of albumin,
keratin 18, hepatocyte nuclear factor 1, Research Institute of Molecular Pathology, A-1030
Vienna, Austria; and § Boehringer Ingelheim, A-1121 Vienna, Austria
-globin, and
erythropoietin, some of which are putative AP-1 target
genes, is not affected. Apoptosis of hematopoietic cells
in mutant livers is most likely not due to a cell-autonomous defect, since c-jun
/ fetal liver cells are able to
reconstitute all hematopoietic compartments of lethally
irradiated recipient mice. A developmental analysis of
chimeras showed contribution of c-jun/ ES cell derivatives to fetal, but not to adult livers, suggesting a role
of c-Jun in hepatocyte turnover. This is in agreement
with the reduced mitotic and increased apoptotic rates
found in primary liver cell cultures derived from c-jun/
fetuses. Furthermore, a novel function for c-Jun was
found in heart development. The heart outflow tract of
c-jun/ fetuses show malformations that resemble the
human disease of a truncus arteriosus persistens. Therefore, the lethality of c-jun mutant fetuses is most likely
due to pleiotropic defects reflecting the diversity of
functions of c-Jun in development, such as a role in
neural crest cell function, in the maintenance of hepatic hematopoiesis and in the regulation of apoptosis.
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