title: BMP signalling regulates the pre-implantation development of extra-embryonic cell lineages in the mouse embryo.
abstract: Pre-implantation development requires the specification and organization of embryonic and extra-embryonic lineages. The separation of these lineages takes place when asymmetric divisions generate inside and outside cells that differ in polarity, position and fate. Here we assess the global transcriptional identities of these precursor cells to gain insight into the molecular mechanisms regulating lineage segregation. Unexpectedly, this reveals that complementary components of the bone morphogenetic protein (BMP) signalling pathway are already differentially expressed after the first wave of asymmetric divisions. We investigate the role of BMP signalling by expressing dominant negative forms of Smad4 and Bmpr2, by downregulating the pathway using RNA interference against BMP ligands and by applying three different BMP inhibitors at distinct stages. This reveals that BMP signalling regulates the correct development of both extra-embryonic lineages, primitive endoderm and trophectoderm, but not the embryonic lineage, before implantation. Together, these findings indicate multiple roles of BMP signalling in the early mouse embryo.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
authors.forename: Sarah J L
authors.initials: SJ
authors.lastname: Graham
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
authors.forename: Krzysztof B
authors.initials: KB
authors.lastname: Wicher
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jedrusik
authors.affiliation: 1] Developmental Cellomics Laboratory, Genome Institute of Singapore, Singapore 138672, Singapore [2] Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Guoji
authors.initials: G
authors.lastname: Guo
authors.affiliation: Developmental Cellomics Laboratory, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Wishva
authors.initials: W
authors.lastname: Herath
authors.affiliation: 1] Developmental Cellomics Laboratory, Genome Institute of Singapore, Singapore 138672, Singapore [2] Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Paul
authors.initials: P
authors.lastname: Robson
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zernicka-Goetz
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D010064:Embryo Implantation; D004707:Endoderm / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D051901:Smad4 Protein; C525820:bmp7 protein, mouse; C498219:Bmpr2 protein, mouse; D052006:Bone Morphogenetic Protein Receptors, Type II