title: Genetic redundancy of GATA factors in the extraembryonic trophoblast lineage ensures the progression of preimplantation and postimplantation mammalian development.
abstract: GATA transcription factors are implicated in establishing cell fate during mammalian development. In early mammalian embryos, GATA3 is selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast fate. However, trophoblast-specific GATA3 function is dispensable for early mammalian development. Here, using dual conditional knockout mice, we show that genetic redundancy ofGata3with paralogGata2in trophoblast progenitors ensures the successful progression of both pre- and postimplantation mammalian development. Stage-specific gene deletion in trophoblasts reveals that loss of both GATA genes, but not either alone, leads to embryonic lethality prior to the onset of their expression within the embryo proper. Using ChIP-seq and RNA-seq analyses, we define the global targets of GATA2/GATA3 and show that they directly regulate a large number of common genes to orchestrate stem versus differentiated trophoblast fate. In trophoblast progenitors, GATA factors directly regulate BMP4, Nodal and Wnt signaling components that promote embryonic-extraembryonic signaling cross-talk, which is essential for the development of the embryo proper. Our study provides genetic evidence that impairment of trophoblast-specific GATA2/GATA3 function could lead to early pregnancy failure.
authors.affiliation: Department of Pathology and Laboratory Medicine and Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Pratik
authors.initials: P
authors.lastname: Home
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Ram Parikshan
authors.initials: RP
authors.lastname: Kumar
authors.affiliation: North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Avishek
authors.initials: A
authors.lastname: Ganguly
authors.affiliation: Department of Pathology and Laboratory Medicine and Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Biswarup
authors.initials: B
authors.lastname: Saha
authors.affiliation: Department of Pathology and Laboratory Medicine and Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Milano-Foster
authors.affiliation: Department of Pathology and Laboratory Medicine and Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Bhaswati
authors.initials: B
authors.lastname: Bhattacharya
authors.affiliation: Department of Pathology and Laboratory Medicine and Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Soma
authors.initials: S
authors.lastname: Ray
authors.affiliation: Department of Molecular and Integrative Physiology, Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Sumedha
authors.initials: S
authors.lastname: Gunewardena
authors.affiliation: Department of Pathology and Laboratory Medicine and Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Arindam
authors.initials: A
authors.lastname: Paul
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Camper
authors.affiliation: Department of Pathology and Laboratory Medicine and Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Fields
authors.affiliation: Department of Pathology and Laboratory Medicine and Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA spaul2@kumc.edu.
authors.forename: Soumen
authors.identifier: 0000-0002-4278-7329
authors.initials: S
authors.lastname: Paul
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D010064:Embryo Implantation; D047108:Embryonic Development; D005260:Female; D050989:GATA2 Transcription Factor / Q000502:physiology*; D050990:GATA3 Transcription Factor / Q000502:physiology*; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D017423:Sequence Analysis, RNA; D013234:Stem Cells / Q000166:cytology*; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse
keywords: GATA2; GATA3; Human; Mammalian development; Mouse; Placenta; Trophoblast stem cells