Temporal BMP4 effects on mouse embryonic and extraembryonic development

• 成果类型: Article
• 署名作者: Hadas, Ron; Rubinstein, Hernan; Mittnenzweig, Markus; Mayshar, Yoav; Ben-Yair, Raz; Cheng, Saifeng; Aguilera-Castrejon, Alejandro; Reines, Netta; Orenbuch, Ayelet-Hashahar; Lifshitz, Aviezer; Chen, Dong-Yuan; Elowitz, Michael B.; Zernicka-Goetz, Magdalena; Hanna, Jacob H.; Tanay, Amos; Stelzer, Yonatan
• 署名单位: Weizmann Institute of Science; Weizmann Institute of Science; Weizmann Institute of Science; California Institute of Technology; University of Cambridge
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6351
• DOI: 10.1038/s41586-024-07937-5
• 发表日期: 2024-10-17
• 关键词: primordial germ-cells; lineage; specification; elf5; allocation; allantois; mesoderm; ectoderm; placenta; defects

摘要

The developing placenta, which in mice originates through the extraembryonic ectoderm (ExE), is essential for mammalian embryonic development. Yet unbiased characterization of the differentiation dynamics of the ExE and its interactions with the embryo proper remains incomplete. Here we develop a temporal single-cell model of mouse gastrulation that maps continuous and parallel differentiation in embryonic and extraembryonic lineages. This is matched with a three-way perturbation approach to target signalling from the embryo proper, the ExE alone, or both. We show that ExE specification involves early spatial and transcriptional bifurcation of uncommitted ectoplacental cone cells and chorion progenitors. Early BMP4 signalling from chorion progenitors is required for proper differentiation of uncommitted ectoplacental cone cells and later for their specification towards trophoblast giant cells. We also find biphasic regulation by BMP4 in the embryo. The early ExE-originating BMP4 signal is necessary for proper mesoendoderm bifurcation and for allantois and primordial germ cell specification. However, commencing at embryonic day 7.5, embryo-derived BMP4 restricts the primordial germ cell pool size by favouring differentiation of their extraembryonic mesoderm precursors towards an allantois fate. ExE and embryonic tissues are therefore entangled in time, space and signalling axes, highlighting the importance of their integrated understanding and modelling in vivo and in vitro. Temporally dynamic extraembryonic and embryonic BMP4 signalling shapes mouse embryo lineage choices.