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Transcriptional regulation by TBX18 in vascular development and disease


Mural cells (pericytes and vascular smooth muscle) enclose blood vessels and are critical for vascular homeostasis.
Absence or malfunction of pericytes or vascular smooth muscle results in aneurysm formation in small or large blood
vessels, respectively. Our previous work showed Tbx18 is selectively expressed in mural cells of multiple adult organs.
Preliminary data indicates that, in mice, ablation of Tbx18 in mural cells results in aortic tortuosity and lethality due to
rupture. These observations led to the hypothesis that transcriptional regulation by TBX18 in mural cells is critical for the
development of functional vascular networks. To fully understand the roles of TBX18 in mural cells and eventually place it
as a gene involved in human vascular disease, we propose to: 1) fully characterize the vascular phenotypes of Pdgfrb-
Cre;Tbx18 mutants; 2) identify genes directly regulated by Tbx18 in mural cells; and 3) test a putative involvement of TBX18
in human aneurysmal diseases.

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