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The PRC2 associated factor Epop is required for Hox genes regulation during axial development in mice

ABSTRACT: The Polycomb repressive complex 2 (PRC2) is an essential modulator of gene repression. We previously reported that in mouse embryonic stem cells (mESCs), PRC2 associates with ElonginB/C through EPOP, allowing for low-level expression of target genes. Here we investigate the role of Epop in vivo by generating a mouse knockout model: we show that Epop null mice are viable and fertile, but display highly penetrant posterior homeotic transformations of the axial skeleton. Consistently, Epop depleted embryos present a shift of the anterior boundary of expression of certain Hox genes. Tissue-specific RNA-seq in embryos suggest that the defect in Hox activation originates already at the level of the presomitic mesoderm (PSM). Overall, our findings indicate that Epop is specifically required for correct body patterning along the antero-posterior axis, by preventing premature activation of the Hox genes.

ORGANISM(S): Mus musculus

PROVIDER: GSE255167 | GEO | 2025/08/19

REPOSITORIES: GEO

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Project description:Within a given vertebrate species, the total number of vertebrae in each anatomical domain is precisely defined and shows little variation among individuals. In contrast, this number can vary tremendously between different species, ranging from as few as six vertebrae in frogs to as many as several hundred in some snakes and fish. Segmental precursors of the vertebrae, called somites are produced sequentially in the embryo from the presomitic mesoderm (PSM), until a final number characteristic of the species, is reached. Here, we show in the chicken embryo that, by controlling the rate of axis elongation, Hox genes control the total number of somites generated by the embryo. We observed that activation of the most posterior Hox genes in somite precursors of the tail bud correlates with an abrupt slowing-down of the speed of axis elongation. We show that progressively more posterior Hox genes, which are collinearly activated in somitic precursors of the epiblast, repress Wnt activity with increasing strength. This leads to a graded repression of the Brachyury/T transcription factor, reducing mesoderm ingression and slowing down the elongation process. Due to the continuation of somite formation, the PSM, which is not fed with sufficient supply of new cells posteriorly, becomes progressively exhausted, ultimately leading to an arrest of segment formation. Our data provide a conceptual framework to explain how the cross-talk between the segmentation clock and the Hox clock accounts for the diversity of vertebral formulae across animal species. Primitive streak aera corresponding to PSM precursors were dissected in Stage 9 somites chicken embryo overexpressing HoxA13 or a control H2B-Venus. The experiment was designed to have biological duplicate in each conditions. The gain-of-function was obtained by electroporating the embryo at Stage 5HH with a vector containing HoxA13 under the CAGGS promoter with an H2B venus reporter. In order to have enough material for the microarray, 7 embryos were pooled in each sample before the hybridization.

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The PRC2 associated factor Epop is required for Hox genes regulation during axial development in mice

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