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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
Author(s) -
Kumar Amit,
Lualdi Margaret,
Loncarek Jadranka,
Cho YoungWook,
Lee JiEun,
Ge Kai,
Kuehn Michael R.
Publication year - 2014
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24125
Subject(s) - biology , gastrulation , ectoderm , microbiology and biotechnology , somite , endoderm , yolk sac , bone morphogenetic protein 4 , embryo , embryogenesis , genetics , bone morphogenetic protein , cellular differentiation , gene
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. Developmental Dynamics 243:937–947, 2014 . © 2014 Wiley Periodicals, Inc.