Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 294

surface to form the epicardium, and then contribute to cardiomyocyte generation
in the ventricular septum and atrial and ventricular walls [ 554 ]. However, adult
TBx18-expressing epicardial cells do not yield cardiomyocytes. TBx18 cardiac

progenitors also create to cardiac fibroblasts and coronary smooth myocytes.
First cells from the proepicardium-epicardium to enter the heart give rise to
cardiomyocytes, whereas subsequent TBx18

+

+ epicardial lineages generate vascular

support cells and fibroblasts.
Growth factors of cardiac myogenesis include members of the bone morpho-
genetic protein and Wnt families. Both canonical and non-canonical Wnt pathways
can promote cardiomyocyte formation. Transcription factor Sox17 acts on transcrip-
tion factors of cardiac specification in primitive mesoderm, mesoderm posterior
homologs MesP1 and MesP2 [ 560 ]. Transcription factor MesP1 is specifically
synthesized in almost all cardiovascular precursors and considered as the earliest
marker of the cardiovascular lineage. Subtype MesP1 targets Dkk1 that impedes
Wnt signaling during cardiovasculogenesis [ 561 ].
Wnt signaling can act as an activator of cardiogenesis in a cell-autonomous
manner (i.e., within the mesoderm) after initial cardiac commitment during discrete
periods of development, although it can also inhibit early cardiac engagement in
a non-cell-autonomous fashion, likely by acting on adjacent endoderm. Canonical
Wnt-

-catenin pathway is required for development and differentiation of cardiac
progenitors of the second heart field [ 562 ]. Wnt signaling upregulates cyclin-D2.
In addition, the Wnt-

β

-catenin signaling exhibits developmental stage-specific
effects not only on cardiomyogenesis, but also on hematopoiesis and vasculo-
genesis [ 563 ]. In the early phase during embryoid body formation, it enhances
differentiation of embryonic stem cells into cardiomyocytes and suppresses dif-
ferentiation into hematopoietic and vascular cell lineages. In the late phase after
embryoid body formation, it prevents bone morphogenetic protein signaling, thus
inhibiting differentiation into cardiomyocytes and enhancing differentiation into
hematopoietic and vascular cell lineages.
Coronary progenitor cells of the proepicardium at the septum transversum near
the venous pole of the heart are responsible for coronary arteriogenesis (but not
formation of the venous system and microvasculature) [ 564 ].

β

-Catenins do not
influence the formation of the proepicardium, migration of proepicardial cells to the
heart, and formation of the primitive epicardium, but participate in the expansion
of the subepicardial space and differentiation of epicardium-derived mesenchymal
cells into coronary smooth myocytes.

β

6.1.9.3 Transcription Factor WT1

Another cardiomyocyte precursor of the epicardium expresses transcription factor
Wilms tumor protein WT1 [ 555 ]. 41 proepicardial cells arise from progen-

itors that express GATA4, Isl1, and NKx2-5. WT1-derived cardiomyocytes are

WT1 +

41 Factor WT1 is expressed in proepicardium and epicardium, but not in myocardium.