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Sox factors transcriptionally regulate ROBO4 gene expression in developing vasculature in zebrafish. J Biol Chem 2011 Sep 02;286(35):30740-7



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Despite their importance as members of the Roundabout (Robo) family in the control of axonal and vascular patterning, the transcriptional regulation of these genes is poorly understood. In this study, we show that members of the Sry-related high mobility box (Sox) transcription factor family as being transcriptional regulators of roundabout4 (robo4), a Robo gene family member that participates in sprouting angiogenesis in vivo, in zebrafish. Double whole mount in situ hybridization analysis in zebrafish embryos revealed co-localization of the vascular relevant Sox factors sox7 or sox18 mRNA with robo4 transcripts in developing intersomitic vessels. A 3-kb human ROBO4 promoter element was able to drive reporter expression in zebrafish to recapitulate the endogenous temporal intersomitic vessel expression pattern of robo4. EMSA analysis confirmed binding of Sox18 to a canonical Sox binding site (from -1170 bp to -1176 bp) in the ROBO4 promoter (3 kb), and mutation analysis indicated that this site was partially responsible for ROBO4 promoter activity in ECs. A combination of gain- and loss-of-function analysis identified Sox7 and Sox18 co-regulation of robo4 but not fli1a transcripts in zebrafish. Finally, Sox-mediated robo4 transcriptional regulation is conserved across evolution. These studies imply Sox-mediated transcriptional regulation of Robo4 in the developing embryonic vasculature.

Author List

Samant GV, Schupp MO, Fran├žois M, Moleri S, Kothinti RK, Chun CZ, Sinha I, Sellars S, Leigh N, Pramanik K, Horswill MA, Remadevi I, Li K, Wilkinson GA, Tabatabai NM, Beltrame M, Koopman P, Ramchandran R


Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Movement
DNA Mutational Analysis
Endothelial Cells
Gene Expression Regulation, Developmental
Neovascularization, Pathologic
Oligonucleotide Array Sequence Analysis
Promoter Regions, Genetic
Receptors, Cell Surface
SOXF Transcription Factors
Transcription, Genetic
Zebrafish Proteins
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d