title: Tril targets Smad7 for degradation to allow hematopoietic specification in Xenopus embryos.
abstract: In Xenopus laevis, bone morphogenetic proteins (Bmps) induce expression of the transcription factor Gata2 during gastrulation, and Gata2 is required in both ectodermal and mesodermal cells to enable mesoderm to commit to a hematopoietic fate. Here, we identify tril as a Gata2 target gene that is required in both ectoderm and mesoderm for primitive hematopoiesis to occur. Tril is a transmembrane protein that functions as a co-receptor for Toll-like receptors to mediate innate immune responses in the adult brain, but developmental roles for this molecule have not been identified. We show that Tril function is required both upstream and downstream of Bmp receptor-mediated Smad1 phosphorylation for induction of Bmp target genes. Mechanistically, Tril triggers degradation of the Bmp inhibitor Smad7. Tril-dependent downregulation of Smad7 relieves repression of endogenous Bmp signaling during gastrulation and this enables mesodermal progenitors to commit to a blood fate. Thus, Tril is a novel component of a Bmp-Gata2 positive-feedback loop that plays an essential role in hematopoietic specification.
authors.affiliation: Department of Neurobiology and Anatomy and Internal Medicine, Division of Hematology and Hematologic Malignancies, University of Utah, School of Medicine, Salt Lake City, UT 84132, USA.
authors.forename: Yangsook Song
authors.initials: YS
authors.lastname: Green
authors.affiliation: Department of Cell and Developmental Biology, Oregon Health and Sciences University, School of Medicine, Portland, OR 97239-3098, USA.
authors.forename: Sunjong
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Department of Cell and Developmental Biology, Oregon Health and Sciences University, School of Medicine, Portland, OR 97239-3098, USA.
authors.forename: Mizuho S
authors.initials: MS
authors.lastname: Mimoto
authors.affiliation: Department of Neurobiology and Anatomy and Internal Medicine, Division of Hematology and Hematologic Malignancies, University of Utah, School of Medicine, Salt Lake City, UT 84132, USA.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Neurobiology and Anatomy and Internal Medicine, Division of Hematology and Hematologic Malignancies, University of Utah, School of Medicine, Salt Lake City, UT 84132, USA jan.christian@neuro.utah.edu.
authors.forename: Jan L
authors.identifier: 0000-0003-3812-3658
authors.initials: JL
authors.lastname: Christian
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008565:Membrane Proteins; D059748:Proteolysis; D051906:Smad7 Protein / Q000378:metabolism*; D029867:Xenopus Proteins / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051906:Smad7 Protein; C000622410:Tril protein, Xenopus; D029867:Xenopus Proteins
keywords: Bmp; Gata2; Primitive hematopoiesis; Smad7; Tril