Primitive to visceral endoderm maturation is essential for mouse epiblast survival beyond implantation
Antonia Weberling,
Dylan Siriwardena,
Christopher Penfold,
Neophytos Christodoulou,
Thorsten E. Boroviak,
Magdalena Zernicka-Goetz
Affiliations
Antonia Weberling
Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Downing Street, Cambridge CB2 3DY, UK
Dylan Siriwardena
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK; Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK
Christopher Penfold
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK; Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK
Neophytos Christodoulou
Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Downing Street, Cambridge CB2 3DY, UK
Thorsten E. Boroviak
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK; Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK
Magdalena Zernicka-Goetz
Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Downing Street, Cambridge CB2 3DY, UK; Plasticity and Self-Organization Group, California Institute of Technology, Division of Biology and Biological Engineering, 1200 E. California Boulevard, Pasadena, CA 91125, USA; Corresponding author
Summary: 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.
