Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 273

6.1.2 Heart Growth Patterns

During cardiogenesis, heart chambers accommodate changes in load associated
with the body's development to fulfil increasing needs. Certain cell subpopulations
participate to a greater extent to cardiogenesis characterized by marked changes
in size (heart chambers having specific dimensions) and tissue architecture. Hence,
cardiogenesis does not follow a gradual expansion during which all involved cardiac
cell types proliferate and contribute equally to heart remodeling and reshaping.
In the zebrafish heart, expansion of the surface area results from proliferation of
a subset of cells from the embryonic wall, each of which creating a muscular patch
of given size and shape. During embryonic maturation, morphogenesis continues
from a primitive structure. The ventricular wall thickens, not by proliferation
of the juvenile wall (original inner layer), but by a new outer layer of muscle
(cortical muscle) generated by some dominant clones of proliferating cells that
may arise from internal trabecular muscle. In fact, cortical cardiomyocytes initially
emerge from internal myofibers that breach the juvenile ventricular wall and
then expand over the surface [ 488 ]. Both inner and outer layers persist in the
adult heart. Therefore, 3 ventriculomyocyte lineages localize to the adult organ:
primordial, trabecular, and cortical myocardial lineage, created in this order from
each other [ 488 ].

6.1.3 Epithelial-Mesenchymal Transition

Epicardium, coronary beds, and conduction paths interact during cardiogenesis.
Cells of the proepicardial organ (PEO), a more or less diffuse cluster of extracardiac
mesothelial cells, are precursors for epicardial epithelial, myocardial connective
tissue, coronary smooth muscle, and endothelial cells. After proliferation, PEO cells
travel over the myocardial surface and differentiate into an epithelium to form the
primitive epicardium. A set of epithelial cells migrate into the subepicardium and
undergo an epithelial-to-mesenchymal transition. 5
Epithelial-to-mesenchymal transformation is implicated in manifold steps of
cardiovascular morphogenesis, such as heart valve development, coronary artery
formation, and inflow and outflow tract septation [ 489 ]. Epithelial-mesenchymal
transition is the first step in morphogenesis that transforms the mesenchyme into
functional structures, such as septa and valves, required for unidirectional pumping
activity.

5 During epithelial-to-mesenchymal transformation, epicardial and endocardial (endothelial) cells
transform into mesenchymal cells that generate different tissues. Epithelial-to-mesenchymal
transformation involves fibroblast growth factor, epidermal growth factor, vascular endothelial
growth factor, transforming growth factor-

β

(Vol. 2 - Chap. 3. Growth Factors), and transcription
factor WT1 encoded by the Wilms tumor-suppressor Wt1 gene.