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Evidence for Hox-specified positional identities in adult vasculature.

Pruett ND, Visconti RP, Jacobs DF, Scholz D, McQuinn T, Sundberg JP, Awgulewitsch A - BMC Dev. Biol. (2008)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA. pruettnd@musc.edu

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.

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Summary of Hoxa3 and Hoxc11 expression domains in major blood vessels as indicated by reporter gene analysis. Left, diagram of the four Hox clusters shown in parallel alignment with arrow at bottom indicating transcriptional orientation and spatial co-linearity of Hox map positions with distinct expression domains along the longitudinal body axis during embryonic development. Right, cartoon of mouse depicting Hoxa3-lacZ (red) and Hoxc11-lacZ (green) zones of expression in major blood vessels.
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Figure 9: Summary of Hoxa3 and Hoxc11 expression domains in major blood vessels as indicated by reporter gene analysis. Left, diagram of the four Hox clusters shown in parallel alignment with arrow at bottom indicating transcriptional orientation and spatial co-linearity of Hox map positions with distinct expression domains along the longitudinal body axis during embryonic development. Right, cartoon of mouse depicting Hoxa3-lacZ (red) and Hoxc11-lacZ (green) zones of expression in major blood vessels.

Mentions: During development, a primary role of Hox genes is thought to "translate" positional information established within a spatial coordinate system into positional identities, which is essential for the differentiation of defined body structures at their appropriate anatomic sites [34]. Once adult structures and organs have formed, a fundamental question arises regarding how their organo-typic shape and physiological properties are being maintained. According to a recently proposed concept this may be achieved by retaining positional identities specified by a Hox code [35,36], which is initially set up during embryonic patterning [37]. This positional identity model was supported by gene expression profiling of human fibroblast populations derived from distinct adult anatomic sites, which revealed that the site-specific Hox profiles mirrored the embryonic Hox patterns relative to the main developmental axes. This was interpreted as evidence for a Hox code-based positional memory underlying the control of topographic fibroblast differentiation [35,36]. The results presented here show complex, yet distinct, spatially restricted Hoxa3 and Hoxc11 patterns in adult blood vessels (see Fig. 9 for a schematic summary) that largely correspond to the embryonic Hoxa3 [23,24] and Hoxc11 [25,28] activity domains. These data are consistent with the positional identity model and support the idea of discrete Hox-specified identities in the vascular network. Validation of this concept in future studies will require a comprehensive analysis of the spatial expression patterns of all 39 Hox genes in the developing and adult cardiovascular system.


Evidence for Hox-specified positional identities in adult vasculature.

Pruett ND, Visconti RP, Jacobs DF, Scholz D, McQuinn T, Sundberg JP, Awgulewitsch A - BMC Dev. Biol. (2008)

Summary of Hoxa3 and Hoxc11 expression domains in major blood vessels as indicated by reporter gene analysis. Left, diagram of the four Hox clusters shown in parallel alignment with arrow at bottom indicating transcriptional orientation and spatial co-linearity of Hox map positions with distinct expression domains along the longitudinal body axis during embryonic development. Right, cartoon of mouse depicting Hoxa3-lacZ (red) and Hoxc11-lacZ (green) zones of expression in major blood vessels.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570687&req=5

Figure 9: Summary of Hoxa3 and Hoxc11 expression domains in major blood vessels as indicated by reporter gene analysis. Left, diagram of the four Hox clusters shown in parallel alignment with arrow at bottom indicating transcriptional orientation and spatial co-linearity of Hox map positions with distinct expression domains along the longitudinal body axis during embryonic development. Right, cartoon of mouse depicting Hoxa3-lacZ (red) and Hoxc11-lacZ (green) zones of expression in major blood vessels.
Mentions: During development, a primary role of Hox genes is thought to "translate" positional information established within a spatial coordinate system into positional identities, which is essential for the differentiation of defined body structures at their appropriate anatomic sites [34]. Once adult structures and organs have formed, a fundamental question arises regarding how their organo-typic shape and physiological properties are being maintained. According to a recently proposed concept this may be achieved by retaining positional identities specified by a Hox code [35,36], which is initially set up during embryonic patterning [37]. This positional identity model was supported by gene expression profiling of human fibroblast populations derived from distinct adult anatomic sites, which revealed that the site-specific Hox profiles mirrored the embryonic Hox patterns relative to the main developmental axes. This was interpreted as evidence for a Hox code-based positional memory underlying the control of topographic fibroblast differentiation [35,36]. The results presented here show complex, yet distinct, spatially restricted Hoxa3 and Hoxc11 patterns in adult blood vessels (see Fig. 9 for a schematic summary) that largely correspond to the embryonic Hoxa3 [23,24] and Hoxc11 [25,28] activity domains. These data are consistent with the positional identity model and support the idea of discrete Hox-specified identities in the vascular network. Validation of this concept in future studies will require a comprehensive analysis of the spatial expression patterns of all 39 Hox genes in the developing and adult cardiovascular system.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA. pruettnd@musc.edu

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.

Show MeSH
Related in: MedlinePlus