Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa

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