title: Essential roles for Cdx in murine primitive hematopoiesis.
abstract: The Cdx transcription factors play essential roles in primitive hematopoiesis in the zebrafish where they exert their effects, in part, through regulation of hox genes. Defects in hematopoiesis have also been reported in Cdx mutant murine embryonic stem cell models, however, to date no mouse model reflecting the zebrafish Cdx mutant hematopoietic phenotype has been described. This is likely due, in part, to functional redundancy among Cdx members and the early lethality of Cdx2 null mutants. To circumvent these limitations, we used Cre-mediated conditional deletion to assess the impact of concomitant loss of Cdx1 and Cdx2 on murine primitive hematopoiesis. We found that Cdx1/Cdx2 double mutants exhibited defects in primitive hematopoiesis and yolk sac vasculature concomitant with reduced expression of several genes encoding hematopoietic transcription factors including Scl/Tal1. Chromatin immunoprecipitation analysis revealed that Scl was occupied by Cdx2 in vivo, and Cdx mutant hematopoietic yolk sac differentiation defects could be rescued by expression of exogenous Scl. These findings demonstrate critical roles for Cdx members in murine primitive hematopoiesis upstream of Scl.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Travis
authors.initials: T
authors.lastname: Brooke-Bisschop
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Joanne G A
authors.initials: JGA
authors.lastname: Savory
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Tanya
authors.initials: T
authors.lastname: Foley
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Randy
authors.initials: R
authors.lastname: Ringuette
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada. Electronic address: dlohnes@uottawa.ca.
authors.forename: David
authors.initials: D
authors.lastname: Lohnes
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis*; D000071616:CDX2 Transcription Factor / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D047108:Embryonic Development / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D015017:Yolk Sac / Q000098:blood supply* / Q000196:embryology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C491272:Cdx1 protein, mouse; C487514:Cdx2 protein, mouse; C489366:Tal1 protein, mouse