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. 2018 Jul 23;7(3):41. doi: 10.3390/biology7030041

Figure 3.

Figure 3

A summary of pre-blastocyst mammalian development with a focus on gene expression. (A) Post-fertilisation but prior to embryonic gene activation (EGA) a loosening of chromatin leads to transcription of the highly repetitive DUX-C genes found in macrosatellite regions. (B) DUX-C protein binding leads to further chromatin opening and transcription of early-EGA target genes. This may require exogenous pyruvate-dependent translocation of mitochondrial TCA enzymes into the nucleus. Binding of the more divergent first homeodomain of DUX-C occurs particularly in the LTR of ERVL-like retrotransposons and leads to species-specific transcription of EGA factors. Binding via the second DUX-C homeodomain in turn activates sets of evolutionarily conserved EGA genes. (C) During main EGA (shown in green), transcription factors previously activated by DUX-C, such as LEUTX in humans, lead to EGA in an increasingly restrictive chromatin environment. (D) Levels or binding kinetics of lineage specific transcription factor protein or transcripts, activated during EGA, show regional heterogeneity due to stochastic (noise) events and leads to a potential bias in lineage, shown by blue for trophoblast and orange for inner cell mass. (E) Formation of apical domains (AD) leads to asymmetry within blastomeres due to tethering of Cdx2 RNA and the YAP-inactivator AMOT. Cells with an AD thus are biased towards a trophoblast fate. (F) In mice, the default state is polarisation: non-polar cells are generated via asymmetrical division. Cells with less AD are biased toward the ICM lineage. In other mammals the default state is non-polar and blastomeres gradually acquire polarity. A relationship between presence of an AD and lineage bias has not yet been examined. (G) Compaction aids the internalisation of non-polar cells to the inside of the embryo. A strong lineage bias is seen. (H) Cells internalised earlier appear to be biased toward the epiblast lineage, those later to the hypoblast lineage. At this stage numerous cells are committed to either TB or ICM-derived lineages while the hypoblast-epiblast lineages within ICM progenitor cells are not yet resolved.