title: Zebrafish Sox7 and Sox18 function together to control arterial-venous identity.
abstract: Sox7 and Sox18 are members of the F-subgroup of Sox transcription factors family and are mostly expressed in endothelial compartments. In humans, dominant mutations in Sox18 are the underlying cause of the severe hypotrichosis-lymphedema-telangiectasia disorder characterized by vascular defects. However little is known about which vasculogenic processes Sox7 and Sox18 regulate in vivo. We cloned the orthologs of Sox7 and Sox18 in zebrafish, analysed their expression pattern and performed functional analyses. Both genes are expressed in the lateral plate mesoderm during somitogenesis. At later stages, Sox18 is expressed in all axial vessels whereas Sox7 expression is mainly restricted to the dorsal aorta. Knockdown of Sox7 or Sox18 alone failed to reveal any phenotype. In contrast, blocking the two genes simultaneously led to embryos displaying dysmorphogenesis of the proximal aorta and arteriovenous shunts, all of which can account for the lack of circulation observed in the trunk and tail. Gene expression analyses performed with general endothelial markers on double morphants revealed that Sox7 and Sox18 are dispensable for the initial specification and positioning of the major trunk vessels. However, morphants display ectopic expression of the venous Flt4 marker in the dorsal aorta and a concomitant reduction of the artery-specific markers EphrinB2a and Gridlock. The striking similarities between the phenotype of Sox7/Sox18 morphants and Gridlock mutants strongly suggest that Sox7 and Sox18 control arterial-venous identity by regulating Gridlock expression.
authors: GIGA-Research - Unité de Biologie Moléculaire et Génie Génétique, Tour B34, Université de Liège, B-4000 Sart Tilman, Belgium. h.pendeville@ulg.ac.be
authors: Hélène
authors: H
authors: Pendeville
authors: Marie
authors: M
authors: Winandy
authors: Isabelle
authors: I
authors: Manfroid
authors: Olivier
authors: O
authors: Nivelles
authors: Patrick
authors: P
authors: Motte
authors: Vincent
authors: V
authors: Pasque
authors: Bernard
authors: B
authors: Peers
authors: Ingrid
authors: I
authors: Struman
authors: Joseph A
authors: JA
authors: Martial
authors: Marianne L
authors: ML
authors: Voz
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001808:Blood Vessels / Q000196:embryology*; D003001:Cloning, Molecular; D016000:Cluster Analysis; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008648:Mesoderm / Q000378:metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D055760:SOXF Transcription Factors; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D055760:SOXF Transcription Factors; D029961:Zebrafish Proteins; C526282:Sox18 protein, zebrafish; C526281:Sox7 protein, zebrafish; C405954:hey2 protein, zebrafish