Research article

Evidence for Hox-specified positional identities in adult vasculature

Nathanael D Pruett¹ , Richard P Visconti² , Donna F Jacobs^1,5 , Dimitri Scholz¹ , Tim McQuinn³ , John P Sundberg⁴ and Alexander Awgulewitsch¹

¹Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA

²Department of Cell Biology and Anatomy, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA

³Department of Pediatrics, Division of Pediatric Cardiology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA

⁴The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA

⁵Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland

author email corresponding author email

BMC Developmental Biology 2008, 8:93doi:10.1186/1471-213X-8-93

Published:	30 September 2008

Abstract

Background

The concept of specifying positional information in the adult cardiovascular system is largely unexplored. While the Hox transcriptional regulators have to be viewed as excellent candidates for assuming such a role, little is known about their presumptive cardiovascular control functions and in vivo expression patterns.

Results

We demonstrate that conventional reporter gene analysis in transgenic mice is a useful approach for defining highly complex Hox expression patterns in the adult vascular network as exemplified by our lacZ reporter gene models for Hoxa3 and Hoxc11. These mice revealed expression in subsets of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) located in distinct regions of the vasculature that roughly correspond to the embryonic expression domains of the two genes. These reporter gene patterns were validated as authentic indicators of endogenous gene expression by immunolabeling and PCR analysis. Furthermore, we show that persistent reporter gene expression in cultured cells derived from vessel explants facilitates in vitro characterization of phenotypic properties as exemplified by the differential response of Hoxc11-lacZ-positive versus-negative cells in migration assays and to serum.

Conclusion

The data support a conceptual model of Hox-specified positional identities in adult blood vessels, which is of likely relevance for understanding the mechanisms underlying regional physiological diversities in the cardiovascular system. The data also demonstrate that conventional Hox reporter gene mice are useful tools for visualizing complex Hox expression patterns in the vascular network that might be unattainable otherwise. Finally, these mice are a resource for the isolation and phenotypic characterization of specific subpopulations of vascular cells marked by distinct Hox expression profiles.