Evidence for Hox-specified positional identities in adult vasculature.
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.


CONCLUSIONS
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.
Pruett
Nathanael D
ND
Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA. pruettnd@musc.edu
Visconti
Richard P
RP
Jacobs
Donna F
DF
Scholz
Dimitri
D
McQuinn
Tim
T
Sundberg
John P
JP
Awgulewitsch
Alexander
A
D000595:Amino Acid Sequence; D000818:Animals; D002319:Cardiovascular System / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D051381:Rats; D046509:Tissue Culture Techniques; D014158:Transcription, Genetic / Q000502:physiology
C489832:HOXA3 protein, human; D018398:Homeodomain Proteins; C080331:Hoxa3 protein, mouse; C111583:Hoxc11 protein, mouse