Scientists identify key genes that initiate embryo development in mice

“For the embryo to develop, the oocyte/egg has to lose its identity and does so by making new stuff. We now know the first steps in how this transition occurs,” said Richard Schultz, a research professor at the university, in an official release.  

Identification of the new genes 

The team lab has identified the OBOX gene family as a plausible candidate. They discovered that this family consists of eight genes (OBOX1-8), with genes OBOX1, 2, 3, 4, 5, and 7 identified as possible candidates for early development. 

The researchers closely examined the role of these genes in a mouse model. 

In the first step, they removed the key genes from the mice. In the next step, they systematically restored the OBOX genes to determine the ones required for zygote genome activation.

The team found that embryo development stops at the two to four-cell stage without these genes. 

“Most interesting, and unanticipated, was that the function of these OBOX genes was highly redundant: a knockout of one could be replaced by another. That redundancy has likely evolved because the transition is so important,” the team mentioned. 

Interestingly, this zygote genome activation is said to be conserved throughout species but with different genes.

In mice, it was found that activation occurs at the two-cell stage. While in human embryos, genome activation happens after the embryo has formed about eight cells. 

However, it is unclear if this same group of OBOX-like genes is implicated in human genome activation. 

“The work also has implications for understanding how embryonic stem cells are reprogrammed so that they can develop into any tissue of the body,” the statement concluded. 

The study was published in the journal Nature.

Study abstract:

Zygotic genome activation (ZGA) activates the quiescent genome to enable the maternal-to-zygotic transition1,2. However, the identity of transcription factors (TFs) that underlie mammalian ZGA in vivo remains elusive. Here, we showed that OBOX, a PRD-like homeobox domain TF family (OBOX1-8)3-5, are key regulators of mouse ZGA. Mice deficient for maternally transcribed Obox1/2/5/7 and zygotically expressed Obox3/4 had a 2-4 cell arrest accompanied by impaired ZGA. Maternal and zygotic OBOX redundantly supported embryonic development as Obox KO defects could be rescued by restoring either of them. Chromatin binding analysis revealed Obox knockout preferentially affected OBOX-binding targets. Mechanistically, OBOX facilitated RNA Pol II “pre-configuration”, as Pol II relocated from the initial 1-cell binding targets to ZGA gene promoters and distal enhancers. The impaired Pol II pre-configuration in Obox mutants was accompanied by defective ZGA and chromatin accessibility transition and aberrant activation of 1-cell Pol II targets. Finally, ectopic expression of OBOX activated ZGA genes and MERVL repeats in mESCs. Hence, these data demonstrate that OBOX regulates murine ZGA and early embryogenesis.