Animal Reproduction Department, INIA, CSIC, Madrid 28404, Spain.
Development. 2024 Oct 15;151(20). doi: 10.1242/dev.202993. Epub 2024 Sep 24.
The first lineage differentiation in mammals gives rise to the inner cell mass and the trophectoderm (TE). In mice, TEAD4 is a master regulator of TE commitment, as it regulates the expression of other TE-specific genes and its ablation prevents blastocyst formation, but its role in other mammals remains unclear. Herein, we have observed that TEAD4 ablation in two phylogenetically distant species (bovine and rabbit) does not impede TE differentiation, blastocyst formation and the expression of TE markers, such as GATA3 and CDX2, although a reduced number of cells in the inner cell mass was observed in bovine TEAD4 knockout (KO) blastocysts. Transcriptional analysis in bovine blastocysts revealed no major transcriptional effect of the ablation, although the expression of hypoblast and Hippo signalling-related genes tended to be decreased in KO embryos. Experiments were conducted in the bovine model to determine whether TEAD4 was required for post-hatching development. TEAD4 KO spherical conceptuses showed normal development of the embryonic disc and TE, but hypoblast migration rate was reduced. At later stages of development (tubular conceptuses), no differences were observed between KO and wild-type conceptuses.
哺乳动物的第一次谱系分化产生了内细胞团和滋养外胚层（TE）。在小鼠中，TEAD4 是 TE 承诺的主要调节因子，因为它调节其他 TE 特异性基因的表达，其缺失阻止囊胚形成，但它在其他哺乳动物中的作用尚不清楚。在此，我们观察到在两个系统发育上较远的物种（牛和兔）中，TEAD4 的缺失并不妨碍 TE 的分化、囊胚形成和 TE 标记物（如 GATA3 和 CDX2）的表达，尽管牛 TEAD4 敲除（KO）囊胚中的内细胞团的细胞数量减少。在牛囊胚中的转录分析显示，消融没有主要的转录效应，尽管 KO 胚胎中胚下和 Hippo 信号相关基因的表达趋于降低。在牛模型中进行了实验以确定 TEAD4 是否对孵化后发育是必需的。TEAD4 KO 球形胚胎显示出胚胎盘和 TE 的正常发育，但胚下细胞迁移率降低。在发育的后期（管状胚胎），KO 和野生型胚胎之间没有观察到差异。
