HOX genes and early mammalian embryogenesis from expression profiles to loss-of-function strategies

HOX proteins are transcription factors controlling cell fate determination in various contexts. Their functions have been well studied in the embryo after gastrulation but a few studies have shown that several HOX transcripts are already present in the mammalian oocyte and embryo until the blastocyst stage suggesting that HOX proteins could also be important factors for the control of the oocyte maturation, the maternal to embryonic transition (including the major onset of the embryonic genome) and/or the first cell lineage segregation. However, their potential roles at that time are totally unexplored. This work had two main goals: the first one was to establish precise expression patterns for several HOX genes in the oocyte and the early embryo until the blastocyst stage. The second one was to investigate HOX functions in this new context. To this end, two mammalian models were used in parallel: the bovine and the mouse. First, systematic expression profiles were established for 7 HOX genes in the bovine and 4 HOX genes in the mouse species. HOX expression patterns seem to be at least partly conserved between both species suggesting that their functions might be conserved as well. Secondly, combining different RT-qPCR strategies we showed that HOX expression in bovine oocytes and early embryos is regulated both at the transcriptional and at the post-transcriptional level reinforcing the idea that they could be important actors of the oocyte maturation and the early mammalian embryo development. Furthermore, our results showed that in bovine embryos, HOXB9 is highly expressed during the maternal to embryonic transition, suggesting HOXB9 to be involved in the activation of the zygotic genome. In order to explore HOXB9 roles in the oocyte and early bovine embryos, loss-of-function strategies based on RNA interference were developed to inactivate HOXB9 transcripts in zygotes but also in immature oocytes and led to a substantial reduction of HOXB9 mRNA.(BIOL 3) -- UCL, 201