Simon Claire S, Garg Vidur, Kuo Ying-Yi, Niakan Kathy K, Hadjantonakis Anna-Katerina
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
bioRxiv. 2024 Jul 24:2024.07.24.604964. doi: 10.1101/2024.07.24.604964.
Cell fate decisions in early mammalian embryos are tightly regulated processes crucial for proper development. While FGF signaling plays key roles in early embryo patterning, its downstream effectors remain poorly understood. Our study demonstrates that the transcription factors and are critical mediators of FGF signaling in cell lineage specification and maturation in mouse embryos. We show that loss of compromises primitive endoderm formation at pre-implantation stages. Furthermore, deficiency delays naïve pluripotency exit and epiblast maturation, leading to elevated NANOG and reduced OTX2 expression within the blastocyst epiblast. As a consequence of delayed pluripotency progression, deficient embryos exhibit anterior visceral endoderm migration defects post-implantation, a process essential for coordinated embryonic patterning and gastrulation initiation. Our results demonstrate the successive roles of these FGF signaling effectors in early lineage specification and embryonic body plan establishment, providing new insights into the molecular control of mammalian development.
早期哺乳动物胚胎中的细胞命运决定是严格调控的过程，对正常发育至关重要。虽然FGF信号在早期胚胎模式形成中起关键作用，但其下游效应器仍知之甚少。我们的研究表明，转录因子 和 是FGF信号在小鼠胚胎细胞谱系特化和成熟中的关键介质。我们发现， 的缺失会损害植入前阶段原始内胚层的形成。此外， 的缺陷会延迟幼稚多能性的退出和外胚层的成熟，导致囊胚外胚层内NANOG表达升高和OTX2表达降低。由于多能性进展延迟， 缺陷的胚胎在植入后表现出内脏内胚层前迁移缺陷，这是协调胚胎模式形成和原肠胚形成起始所必需的过程。我们的结果证明了这些FGF信号效应器在早期谱系特化和胚胎体轴建立中的连续作用，为哺乳动物发育的分子控制提供了新的见解。
