title: BMP receptor IA is required in the mammalian embryo for endodermal morphogenesis and ectodermal patterning.
abstract: BMPRIA is a receptor for bone morphogenetic proteins with high affinity for BMP2 and BMP4. Mouse embryos lacking Bmpr1a fail to gastrulate, complicating studies on the requirements for BMP signaling in germ layer development. Recent work shows that BMP4 produced in extraembryonic tissues initiates gastrulation. Here we use a conditional allele of Bmpr1a to remove BMPRIA only in the epiblast, which gives rise to all embryonic tissues. Resulting embryos are mosaics composed primarily of cells homozygous null for Bmpr1a, interspersed with heterozygous cells. Although mesoderm and endoderm do not form in Bmpr1a null embryos, these tissues are present in the mosaics and are populated with mutant cells. Thus, BMPRIA signaling in the epiblast does not restrict cells to or from any of the germ layers. Cells lacking Bmpr1a also contribute to surface ectoderm; however, from the hindbrain forward, little surface ectoderm forms and the forebrain is enlarged and convoluted. Prechordal plate, early definitive endoderm, and anterior visceral endoderm appear to be expanded, likely due to defective morphogenesis. These data suggest that the enlarged forebrain is caused in part by increased exposure of the ectoderm to signaling sources that promote anterior neural fate. Our results reveal critical roles for BMP signaling in endodermal morphogenesis and ectodermal patterning.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham NC 27710, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Davis
authors.forename: Shigeto
authors.initials: S
authors.lastname: Miura
authors.forename: Christin
authors.initials: C
authors.lastname: Hill
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishina
authors.forename: John
authors.initials: J
authors.lastname: Klingensmith
mesh_terms: D000818:Animals; D019521:Body Patterning; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002490:Central Nervous System / Q000033:anatomy & histology / Q000196:embryology; D004475:Ectoderm / Q000166:cytology / Q000502:physiology*; D004622:Embryo, Mammalian / Q000502:physiology*; D004625:Embryo, Nonmammalian; D004707:Endoderm / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D009024:Morphogenesis; D009030:Mosaicism; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology
chemical_list: D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; C484194:Meox2 protein, mouse; D017978:Receptors, Growth Factor; D017346:Protein Serine-Threonine Kinases; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I