Functional analysis of Gm11545 in lineage specification during preimplantation embryogenesis in mice

Abstract

After fertilization, embryos undergo continuous cleavage, leading to the first cell fate decision, known as the first lineage specification. This process is tightly regulated by various molecular mechanisms, including the Hippo signaling pathway. Despite extensive research, the exact regulatory mechanisms governing the first lineage specification remain unclear. In this study, I investigated the role of an unnamed gene, designated Gm11545, in early embryogenesis, particularly its involvement in the Hippo signaling pathway during the first cell lineage specification in mouse embryos. Knockdown (KD) of Gm11545 led to an increase in cytoplasmic F-actin meshwork in the outer blastomeres of the morula, which caused the cytoplasmic localization of angiomotin (AMOT) and a reduction in nuclear yes-associated protein (YAP) localization. Consequently, caudal type homeobox 2 (CDX2) expression, a critical transcription factor for trophectoderm differentiation, was downregulated, ultimately leading to failure in blastocyst formation. Additionally, in blastocysts developed from chimeric morulae of which each embryo contains both normal and KD blastomeres, Gm11545 KD blastomeres were predominantly localized in the inner cell mass (ICM) region, suggesting that Gm11545 plays a significant role in promoting trophectoderm (TE) specification. These findings highlight Gm11545 as a crucial regulator of asymmetric Hippo signaling between inner and outer blastomeres, influencing cell fate decisions during the first lineage specification in embryogenesis. Keywords Embryo, lineage specification, Gm11545, Hippo pathway