Pbx1-dependent control of VMC differentiation kinetics underlies gross renal vascular patterning.

ABSTRACT: The architecture of an organ's vascular bed subserves its physiological function and metabolic demands. However, the mechanisms underlying gross vascular patterning remain elusive. Using intravital dye labeling and 3D imaging, we discovered that systems-level vascular patterning in the kidney is dependent on the kinetics of vascular mural cell (VMC) differentiation. Conditional ablation of the TALE transcription factor Pbx1 in renal VMC progenitors in the mouse led to the premature upregulation of PDGFRβ, a master initiator of VMC-blood vessel association. This precocious VMC differentiation resulted in nonproductive angiogenesis, abnormal renal arterial tree patterning and neonatal death consistent with kidney dysfunction. Notably, we establish that Pbx1 directly represses Pdgfrb, and dem

SUBMITTER: Hurtado R 

PROVIDER: S-EPMC4529034 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature