Abstract:
The GCM family of transcription factors consists of Drosophila melanogaster GCM, an important regulator
of gliogenesis in the fly, and its two mammalian homologs, GCMa and GCMb. To clarify the function of these
mammalian homologs, we deleted GCMa in mice. Genetic ablation of murine GCMa (mGCMa) is embryonic
lethal, with mice dying between 9.5 and 10 days postcoitum. At the time of death, no abnormalities were
apparent in the embryo proper. Nervous system development, in particular, was not impaired, as might have
been expected in analogy to Drosophila GCM. Instead, placental failure was the cause of death. In agreement
with the selective expression of mGCMa in labyrinthine trophoblasts, mutant placentas did not develop a
functional labyrinth layer, which is necessary for nutrient and gas exchange between maternal and fetal blood.
Only a few fetal blood vessels entered the placenta, and these failed to thrive and branch normally. Labyrinthine
trophoblasts did not differentiate. All other layers of the placenta, including spongiotrophoblast and
giant cell layer, formed normally. Our results indicate that mGCMa plays a critical role in trophoblast
differentiation and the signal transduction processes required for normal vascularization of the placenta