Evolution and expression of Glial Cells Missing (GCM1 and GCM2) in monotremes suggests an ancient role in reproduction and placentation

Abstract

The Glial Cells Missing (GCM) genes were first discovered in Drosophila and encode transcription factors important for gliogenesis. In placental mammals, GCM1 regulates several genes that are important for early placenta development, while its paralog GCM2 is important for parathyroid gland development. The egg-laying monotremes, which represent the most diverged extant mammalian lineage, undergo a short period of intrauterine development and form a simple placenta. To gain more insight into the evolution of GCM genes we analysed the sequence, expression, and genomic localization of GCM1 and GCM2 genes in the platypus and echidna. We found that the chromosomal localisation of GCM1 changed after the divergence of therian mammals, coinciding with the evolution of a complex placenta. Expression analysis revealed the presence of GCM transcripts in male and female monotreme gonads, as well as expression of GCM1 in the female reproductive tract. GCM binding sites in target genes associated with placental development in therian mammals were also present in the monotremes and the chicken. Together, this suggests that the role of GCM1 in the placenta emerged early in mammalian evolution.