Primitive to visceral endoderm maturation is essential for mouse epiblast survival beyond implantation.

Weberling A., Siriwardena D., Penfold C., Christodoulou N., Boroviak TE., Zernicka-Goetz M.

The implantation of the mouse blastocyst initiates a complex sequence of tissue remodeling and cell differentiation events required for morphogenesis, during which the extraembryonic primitive endoderm transitions into the visceral endoderm. Through single-cell RNA sequencing of embryos at embryonic day 5.0, shortly after implantation, we reveal that this transition is driven by dynamic signaling activities, notably the upregulation of BMP signaling and a transient increase in Sox7 expression. Embryos deficient in Hepatocyte nuclear factor-1-beta (Hnf1b-/-), a gene critical for visceral endoderm differentiation, showed an interaction between visceral endoderm and epiblast, crucial for epiblast survival. Single-cell RNA profiling of Hnf1b-/- visceral endoderm shows developmental delays and severe dysregulation in several nutrient transport pathways. Impaired glucose uptake in Hnf1b-/- embryos suggests that the activation of nutrient transport mechanisms during the primitive-to-visceral endoderm transition may be vital for post-implantation epiblast development. These findings offer new insights into the molecular regulation of early mammalian development.

DOI

10.1016/j.isci.2024.111671

Type

Journal article

Publication Date

2025-01-17T00:00:00+00:00

Volume

28

Keywords

Biological sciences, Cell biology, Developmental biology, Embryology, Natural sciences

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