Identification of integrin-alpha4, Rb1, and syncytin a as murine placental target genes of the transcription factor GCMa/Gcm1.

Members of the GCM (glial cells missing) transcription factor family have been shown to act as master regulators in different cells during mammalian and fly development being responsible for processes including gliogenesis, hematopoiesis, placental formation, and development of the parathyroidea. In the central nervous system of flies, several target genes for GCM have been reported, namely repo, pointed, and tramtrack. In mammals, two GCM genes are known (GCMa and GCMb), but the knowledge of their target genes is very limited. Here, we present for the first time a global approach aimed to identify GCMa target genes. We found 66 genes up-regulated and 11 genes down-regulated in GCMa-deficient chorionic tissue of mice at embryonic day 9.5. Moreover, we verified by quantitative reverse transcription-PCR all 11 down-regulated genes. The two most strongly down-regulated genes, integrin-alpha4 and retinoblastoma (Rb1), were further analyzed by promoter studies. Additionally, we identified down-regulation of the murine syncytin A gene, which is fundamental for syncytiotrophoblast formation. Finally, we proved strong down-regulation of integrin-alpha4 and Rb1 transcript levels by in situ hybridization in murine GCMa-deficient placentae at embryonic day 9.5. Our data demonstrate for the first time that genes encoding key regulators of placental tissue formation and architecture are regulated by GCMa.