ABSTRACT
Effective establishment of the hematopoietic and vascular systems is prerequisite for successful embryogenesis. The ETS transcription factor Etv2 has proven to be essential for hematopoietic and vascular development. Etv2 expression marks the onset of the hematopoietic and vascular development and its deficiency leads to an absolute block in hematopoietic and vascular development. Etv2 is transiently expressed during development and is mainly expressed in testis in adults. Consistent with its expression pattern, Etv2 is transiently required for the generation of the optimal levels of the hemangiogenic cell population. Deletion of this gene after the hemangiogenic progenitor formation leads to normal hematopoietic and vascular development. Mechanistically, ETV2 induces the hemangiogenic program by activating blood and endothelial cell lineage specifying genes and enhancing VEGF signaling. Moreover, ETV2 establishes an ETS hierarchy by directly activating other Ets genes, which in the face of transient Etv2 expression, presumably maintain blood and endothelial cell program initiated by ETV2 through an ETS switching mechanism. Current studies suggest that the hemangiogenic progenitor population is exclusively sensitive to ETV2-dependent FLK1 signaling. Any perturbation in the ETV2, VEGF, and FLK1 balance causing insufficient hemangiogenic progenitor cell generation would lead to defects in hematopoietic and endothelial cell development.
Subject(s)
Blood Vessels/embryology , Hematopoietic Stem Cells/physiology , Transcription Factors/metabolism , Animals , Blood Vessels/cytology , Cell Lineage , Endothelial Cells/physiology , Gene Expression Regulation, Developmental , Humans , Transcription Factors/genetics , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolism , Xenopus Proteins/genetics , Xenopus Proteins/metabolismSubject(s)
Body Patterning/genetics , Gastrula/metabolism , Morpholines/metabolism , Oligonucleotides, Antisense/metabolism , Receptors, Cell Surface/metabolism , Receptors, G-Protein-Coupled , Xenopus laevis/embryology , Activins/pharmacology , Animals , Body Patterning/drug effects , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/embryology , Embryo, Nonmammalian/metabolism , Gastrula/drug effects , Gene Expression Regulation, Developmental , Oligonucleotides, Antisense/genetics , Phenotype , Receptors, Cell Surface/genetics , Xenopus Proteins/genetics , Xenopus Proteins/metabolism , Xenopus laevis/genetics , Xenopus laevis/growth & developmentSubject(s)
Body Patterning/genetics , Morpholines/metabolism , Oligonucleotides, Antisense/metabolism , Receptors, Neurotransmitter/metabolism , Zebrafish/embryology , Zebrafish/genetics , Amino Acid Sequence , Animals , Embryo, Nonmammalian/embryology , Embryo, Nonmammalian/metabolism , Evolution, Molecular , Gene Expression Regulation, Developmental , Molecular Sequence Data , Oligonucleotides, Antisense/genetics , Phenotype , Receptors, Neurotransmitter/chemistry , Receptors, Neurotransmitter/genetics , Zebrafish/growth & development , Zebrafish Proteins/chemistry , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolismABSTRACT
We have isolated a new Wnt receptor frizzled family member from Xenopus laevis, Xenopus frizzled-5 (Xfz5), a likely ortholog of human frizzled-5. Based on Northern and whole-mount in situ hybridization data, Xfz5 is first detected at the late neurula stage in retinal primordia. Throughout the tailbud stage Xfz5 is expressed exclusively in the neural retina within the optic vesicles. During tadpole stage Xfz5 expression becomes restricted to the ciliary marginal zone. This highly restrictive expression pattern makes Xfz5 an excellent marker for neural retinal tissue.
Subject(s)
Eye Proteins/biosynthesis , Eye/embryology , Retina/embryology , Xenopus/metabolism , Amino Acid Sequence , Animals , Blotting, Northern , Frizzled Receptors , In Situ Hybridization , Molecular Sequence Data , Phylogeny , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Time Factors , Tissue Distribution , Xenopus ProteinsABSTRACT
We have isolated one member of the frizzled family of wnt receptors from Xenopus (Xfz7) to study the role of cell-cell communication in the establishment of the vertebrate axis. We demonstrate that this maternally encoded protein specifically synergizes with wnt proteins in ectopic axis induction. Embryos derived from oocytes depleted of maternal Xfz7 RNA by antisense oligonucleotide injection are deficient in dorsoanterior structures. Xfz7-depleted embryos are deficient in dorsal but not ventral mesoderm due to the reduced expression of the wnt target genes siamois, Xnr3 and goosecoid. These signaling defects can be restored by the addition of beta-catenin but not Xwnt8b. Xfz7 thus functions upstream of the known GSK-3/axin/beta-catenin intracellular signaling complex in vertebrate dorsoventral mesoderm specification.
Subject(s)
Cytoskeletal Proteins/genetics , Proto-Oncogene Proteins/metabolism , Receptors, Cell Surface/genetics , Receptors, G-Protein-Coupled , Repressor Proteins , Trans-Activators , Transcription Factors , Xenopus Proteins , Xenopus/embryology , Zebrafish Proteins , Amino Acid Sequence , Animals , Body Patterning , Evolution, Molecular , Gene Expression Regulation, Developmental , Goosecoid Protein , Homeodomain Proteins/genetics , Mesoderm/metabolism , Microinjections , Molecular Sequence Data , Oocytes/metabolism , RNA, Antisense/pharmacology , RNA, Messenger/metabolism , Receptors, Cell Surface/metabolism , Signal Transduction , Transforming Growth Factor beta/genetics , Wnt Proteins , beta CateninABSTRACT
We have used zebrafish as a model system for the study of vertebrate dorsoventral patterning. We isolated a maternally expressed and dorsal organizer localized member of the frizzled family of wnt receptors. Wild-type and dominant, loss-of-function molecules in misexpression studies demonstrate frizzled function is necessary and sufficient for dorsal mesoderm specification. frizzled activity is antagonized by the action of GSK-3, and we show GSK-3 is also required for zebrafish dorsal mesoderm formation. frizzled cooperatively interacts with the maternally encoded zebrafish wnt8 protein in dorsal mesodermal fate determination. This frizzled -mediated wnt pathway for dorsal mesoderm specification provides the first evidence for the requirement of a wnt-like signal in vertebrate axis determination.
