ETV4 and ETV5 orchestrate FGF-mediated lineage specification and epiblast maturation during early mouse development.

IF 3.7 2区 生物学 Q1 DEVELOPMENTAL BIOLOGY
Development Pub Date : 2025-03-15 Epub Date: 2025-03-24 DOI:10.1242/dev.204278
Claire S Simon, Woonyung Hur, Vidur Garg, Ying-Yi Kuo, Kathy K Niakan, Anna-Katerina Hadjantonakis
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引用次数: 0

Abstract

Cell fate decisions in early mammalian embryos are tightly regulated processes crucial for proper development. While FGF signalling plays key roles in early embryo patterning, its downstream effectors remain poorly understood. Our study demonstrates that the transcription factors Etv4 and Etv5 are crucial mediators of FGF signalling in cell lineage specification and maturation in mouse embryos. We show that loss of Etv5 compromises primitive endoderm formation at pre-implantation stages. Furthermore, Etv4 and Etv5 (Etv4/5) 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, Etv4/Etv5-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 signalling effectors in early lineage specification and embryonic body plan establishment, providing new insights into the molecular control of mammalian development.

在小鼠早期发育过程中,ETV4和ETV5协调fgf介导的谱系规范和外胚层成熟。
早期哺乳动物胚胎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中起着关键作用,但其下游效应仍然知之甚少。我们的研究表明,转录因子Etv4和Etv5是小鼠胚胎细胞系分化和成熟过程中FGF信号传导的关键介质。我们发现Etv5的缺失损害了着床前阶段原始内胚层的形成。此外,Etv4/5缺陷延迟naïve多能性退出和外胚层成熟,导致胚泡外胚层内NANOG升高和OTX2表达降低。由于多能性进展延迟,Etv4/5缺陷胚胎在着床后表现出前内脏内胚层迁移缺陷,这是协调胚胎模式和原肠胚形成的必要过程。我们的研究结果证明了这些FGF信号效应因子在早期谱系规范和胚胎体计划建立中的连续作用,为哺乳动物发育的分子控制提供了新的见解。
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来源期刊
Development
Development 生物-发育生物学
CiteScore
6.70
自引率
4.30%
发文量
433
审稿时长
3 months
期刊介绍: Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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