title: Loss of function of mouse Pax-Interacting Protein 1-associated glutamate rich protein 1a (Pagr1a) leads to reduced Bmp2 expression and defects in chorion and amnion development.
abstract: BACKGROUND
  Human PAX-Interacting Protein 1 (PAXIP1)-associated glutamate rich protein 1 (PAGR1, also known as PA1) originally was discovered as part of a complex containing PAXIP1 and histone H3K4 methyltransferases MLL3 and MLL4, suggesting a role in epigenetic gene regulation. Further in vitro studies suggested additional functions in DNA damage repair and transcription. However, in vivo analysis of PAGR1 function has been lacking.
  
  
  RESULTS
  Here we show that expression of the cognate mouse gene Pagr1a is found predominately in the extraembryonic and chorionic ectoderm from pregastrulation stages and is up-regulated within the embryo proper after gastrulation. Embryos with a germ line deletion of Pagr1a establish the anterior-posterior axis, and show normal neuroectodermal, mesodermal, and endodermal patterning, but fail to develop beyond the four- to five-somite stage or to undergo axial rotation. Pagr1a(-) (/) (-) embryos also show abnormal development of extraembryonic tissues with defects seen in the amnion, chorion and visceral yolk sac. At the molecular level, Pagr1a(-) (/) (-) embryos have reduced expression of BMP2, a known regulator of extraembryonic development.
  
  
  CONCLUSIONS
  Loss of mouse Pagr1a function leads to defective extraembryonic development, likely due at least in part to altered BMP signaling, contributing to developmental arrest.
authors.affiliation: Laboratory of Protein Dynamics and Signaling, National Cancer Institute, National Institutes of Health, Frederick, Maryland.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Margaret
authors.initials: M
authors.lastname: Lualdi
authors.forename: Jadranka
authors.initials: J
authors.lastname: Loncarek
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Cho
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Kai
authors.initials: K
authors.lastname: Ge
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kuehn
mesh_terms: D000650:Amnion / Q000378:metabolism*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D002823:Chorion / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D051379:Mice
chemical_list: D055396:Bone Morphogenetic Protein 2
keywords: BMP signaling; amniochorionic fold; amnion; chorion