Radial Construction of an Arterial Wall

Abstract

SUMMARY Some of the most serious diseases involve altered size and structure of the arterial wall. Elucidating how arterial walls are built could aid understanding of these diseases, but little is known about how concentric layers of muscle cells and the outer adventitial layer are assembled and patterned around endothelial tubes. Using histochemical, clonal, and genetic analysis in mice, here we show that the pulmonary artery wall is constructed radially, from the inside out, by two separate but coordinated processes. One is sequential induction of successive cell layers from surrounding mesenchyme. The other is controlled invasion of outer layers by inner layer cells through developmentally-regulated cell reorientation and radial migration. We propose that a radial signal gradient controls these processes and provide evidence that PDGF-B and at least one other signal contribute. Modulation of such radial signaling pathways may underlie vessel-specific differences and pathological changes in arterial wall size and structure.

Transcription factor TBX4 regulates myofibroblast accumulation and lung fibrosis

“…Tbx4lineage cells include lipofibroblasts and a few endothelial cells (Figure 1, G and H). These results are consistent with recent data indicating that Tbx4-Cre labels undifferentiated mesenchyme, airway smooth muscle, vascular smooth muscle, and mesothelium (22,26,27). The locations of tdTomatolabeled (tdTlabeled) cells were identical in the lungs of both strains.…”

Diverse cellular architecture of atherosclerotic plaque derives from clonal expansion of a few medial SMCs

“…The clonal pattern of the murine aortic media is consistent with the developmental processes described for the murine pulmonary artery, where intermixing of cells occurs during recruitment and differentiation of SMCs along the nascent endothelium (11). Curiously, this is very different from the pattern reported for human aortas and coronary arteries, proposed to have large coherent patches of SMCs deriving from the same embryonic ancestor cells (9,10).…”

Pdgfrb‐Cre targets lymphatic endothelial cells of both venous and non‐venous origins

“…The Pdgfrb‐Cre line (Foo et al ., 2006), where Cre recombinase expression is driven by a transgenic fragment of the gene for platelet‐derived growth factor receptor β ( Pdgfrb ), has been used extensively to specifically target mural cells, namely vascular smooth muscle cells, pericytes and hepatic stellate cells; examples are given in ref (Abraham et al ., 2008; Foo et al ., 2006; Greif et al ., 2012; Henderson et al ., 2013; Jeansson et al ., 2011; Kogata et al ., 2009; Siegenthaler et al ., 2013; Stenzel et al ., 2009; Ye et al ., 2009; You et al ., 2014). We (Stanczuk et al ., 2015) and others (Klotz et al ., 2015) recently showed that Pdgfrb‐Cre unexpectedly also targets a large proportion of embryonic lymphatic endothelial cells (LECs) in the developing mesentery (Stanczuk et al ., 2015) and the heart (Klotz et al ., 2015).…”