Nodal cis-regulatory elements reveal epiblast and primitive endoderm heterogeneity in the peri-implantation mouse embryo |
| |
Authors: | Granier Céline Gurchenkov Vasily Perea-Gomez Aitana Camus Anne Ott Sascha Papanayotou Costis Iranzo Julian Moreau Anne Reid John Koentges Georgy Sabéran-Djoneidi Délara Collignon Jérôme |
| |
Affiliation: | aUniversité Paris-Diderot, CNRS, Institut Jacques Monod, UMR 7592, Development and Neurobiology programme, F-75013 Paris, France;bLaboratory of Functional Genomics, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK |
| |
Abstract: | Nodal, a secreted factor known for its conserved functions in cell-fate specification and the establishment of embryonic axes, is also required in mammals to maintain the pluripotency of the epiblast, the tissue that gives rise to all fetal lineages. Although Nodal is expressed as early as E3.5 in the mouse embryo, its regulation and functions at pre- and peri-implantation stages are currently unknown. Sensitive reporter transgenes for two Nodal cis-regulatory regions, the PEE and the ASE, exhibit specific expression profiles before implantation. Mutant and inhibitor studies find them respectively regulated by Wnt/β-catenin signaling and Activin/Nodal signaling, and provide evidence for localized and heterogeneous activities of these pathways in the inner cell mass, the epiblast and the primitive endoderm. These studies also show that Nodal and its prime effector, FoxH1, are not essential to preimplantation Activin/Nodal signaling. Finally, a strong upregulation of the ASE reporter in implanting blastocysts correlates with a downregulation of the pluripotency factor Nanog in the maturing epiblast. This study uncovers conservation in the mouse blastocyst of Wnt/β-catenin and Activin/Nodal-dependent activities known to govern Nodal expression and the establishment of polarity in the blastula of other deuterostomes. Our results indicate that these pathways act early on to initiate distinct cell-specification processes in the ICM derivatives. Our data also suggest that the activity of the Activin/Nodal pathway is dampened by interactions with the molecular machinery of pluripotency until just before implantation, possibly delaying cell-fate decisions in the mouse embryo. |
| |
Keywords: | Mouse blastocyst Epiblast Primitive endoderm Heterogeneity Nodal Nanog |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|