The placenta is an extraordinarily variable organ with diverse morphology, complexity, and invasiveness exhibited across mammals. Even the egg-laying monotremes undergo a short intra-uterine gestation during which they develop a simple yolk-sac placenta. Analysis of genes involved in placentation provides valuable insight into the reproductive biology of monotremes and the evolution of the mammalian placenta. In therian mammals, the transcription factor GCM1 is expressed in the kidney and placenta where it is essential for placental development and gives rise to cell types governing invasiveness. We analysed the sequence, chromosomal localisation, expression, and target genes of GCM1 and its homologue GCM2 in the platypus and echidna.
Synteny analysis revealed that the chromosomal location of GCM1 shifted after the divergence of monotremes, coinciding with the emergence of more complex placentae in therian mammals. Despite this shift, we observed high sequence conservation of the GCM1 DNA binding domain and transactivation domains across monotremes, therian mammals, and birds. RT-PCR and RNA in-situ hybridisation revealed expression of GCM1 in the active reproductive tract in the platypus and echidna. Surprisingly, we also discovered co-expression of GCM1 and GCM2 in the platypus ovary, suggesting a species-specific function in this tissue. Analysis of orthologous therian, monotreme, and avian target genes revealed conservation of GCM1 binding sites, suggesting that the regulatory network between GCM1 and its targets was established prior to the evolution of the mammalian placenta.
Together, our results suggest that GCM1 was involved in reproduction prior to gaining the placental development and invasion functions observed in therian mammals. The chromosomal relocation of GCM1 in therian mammals may have resulted in an altered genetic environment, contributing to its emerging function in placental development. We are currently undertaking transcriptome analysis of the monotreme reproductive tract which will provide a broader picture of the molecular pathways involved in monotreme placentation.