Wnt11 and Wnt7a are up‐regulated in association with differentiation of cardiac conduction cells in vitro and in vivo

Abstract

The heart beat is coordinated by a precisely timed sequence of action potentials propagated through cells of the conduction system. Previously, we have shown that conduction cells in the chick embryo are derived from multipotent, cardiomyogenic progenitors present in the looped, tubular heart. Moreover, analyses of heterogeneity within myocyte clones and cell birth dating have indicated that elaboration of the conduction system occurs by ongoing, localized recruitment from within this multipotent pool. In this study, we have focused on a potential role for Wnt signaling in development of the cardiac conduction system. Treatment of embryonic myocytes from chick with endothelin-1 (ET-1) has been shown to promote expression of markers of Purkinje fiber cells. By using this in vitro model, we find that Wnt11 are Wnt7a are up-regulated in association with ET-1 treatment. Moreover, in situ hybridization reveals expression, although not temporal coincidence of, Wnt11 and Wnt7a in specialized tissues in the developing heart in vivo. Specifically, whereas Wnt11 shows transient and prominent expression in central elements of the developing conduction system (e.g., the His bundle), relative increases in Wnt7a expression emerge at sites consistent with the location of peripheral conduction cells (e.g., subendocardial Purkinje fibers). The patterns of Wnt11 and Wnt7a expression observed in vitro and in the embryonic chick heart appear to be consistent with roles for these two Wnts in differentiation of cardiac conduction tissues.

Wnt11 Signaling Promotes Proliferation, Transformation, and Migration of IEC6 Intestinal Epithelial Cells

“…Here we show that Wnt11 mRNA is present in various mouse tissues such as the heart and kidney as reported previously (50,78). The distribution of Wnt11 in these tissues corresponds well with its functions in the morphogenesis of cardiac myocytes (46) and differentiation of cardiac conduction cells (78) and kidney ureter (50,79). In the developing gastrointestinal tract, Wnt11 is localized in the endodermal layer of the esophagus and colon as well as in the mesenchymal layer of the stomach (20).…”

“…The source and the nature of the Wnt signal in the intestinal crypt and whether a concentration gradient of Wnt secretion exists in the intestinal crypt are still largely undetermined. Here we show that Wnt11 mRNA is present in various mouse tissues such as the heart and kidney as reported previously (50,78). The distribution of Wnt11 in these tissues corresponds well with its functions in the morphogenesis of cardiac myocytes (46) and differentiation of cardiac conduction cells (78) and kidney ureter (50,79).…”

The Multiple Phases and Faces of Wnt Signaling During Cardiac Differentiation and Development

“…Heart valve formation Required (zebrafish, chicken) [96][97][98][99][100] Not known Development of conduction system Not known Expression but no functional data 121 The role of different aspects of the Wnt signaling network during cardiac differentiation and development are given as discussed in the text.…”

Reprogramming the Beat

“…Beginning with the observations that peripheral and central conduction tissue derives from cardiomyocyte progenitors in the chick, 3,4 investigators have now identified key roles for many important molecular signals and transcription factors in conduction system development. Signaling molecules implicated in the formation of the conduction system include endothelin, [5][6][7][8][9] neuregulin, 10 -13 Wnts, 14 and bone morphogenetic proteins, 15 and complex transcriptional roles have been identified for NKx2.5, 16 -20 members the T-box transcription factor family, 18,21,22 shox2, 23 msx2, 24,25 and hop. 26 -28 In this issue of Circulation, Rentschler et al 29 take a significant step toward understanding the determinants of conduction cell fate.…”