Roles of Structural maintenance of chromosome flexible domain containing 1 (Smchd1) in early lineage formation and development in mice

The function of Structural maintenance of chromosome flexible domain containing 1 (Smchd1) was examined during mouse preimplantation development using an siRNA knockdown approach. Transient SMCHD1 deficiency during the period between fertilization and morula/early blastocyst stage compromised embryo viability and resulted in reduced cell number, reduced embryo diameter, and reduced nuclear volumes at the morula stage. RNAseq analysis of Smchd1 knockdown morulae revealed aberrant increases in expression of mRNAs related to the trophoblast lineage, indicating SMCHD1 inhibits trophoblast lineage gene expression and promotes inner cell mass formation. siRNA knockdown also reduced expression of cell proliferation genes, including S-phase kinase-associated protein 2 (Skp2). Smchd1 expression was elevated in Caudal type homeobox transcription factor 2 (Cdx2)-/- blastocysts, indicating enriched expression, and further indicating a role in inner cell mass development. These results indicate that Smchd1 plays dual roles in the preimplantation embryo, promoting a lineage-appropriate pattern of gene expression supporting inner cell mass formation, whilst controlling lineage formation and gene expression in the trophectoderm. Overall design: Effects of SMCHD1 siRNA knockdown were tested in mouse embryos

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Midic U, Vincent KA, Wang K, Lokken A, Severance AL, Ralston A, Knott JG, Latham KE