Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 272

Tabl e 6. 2. Examples of signaling molecules involved in cardiac specification (Source: [ 486 ];
FGF: fibroblast growth factor; GATA: DNA sequence GATA-binding transcrition factor; Myocd:
myocardin; NKx2: NK2 transcription factor-related homeobox protein; SHh: sonic Hedgehog;
SRF: serum response factor; TBx: T-box transcription factor; TH: tyrosine hydroxylase). Inhibitors
of bone morphogenetic proteins (BMP) — noggin and chordin — secreted from the notochord
limit the amount of developing cardiac tissue. They also retard the differentiation of a population of
cardiac precursors that will form the outflow and inflow tracts of the mature heart. Cerberus-related
protein is an extracellular, multivalent antagonist that binds to growth factors of the transforming
growth factor (TGF β ) superfamily, Nodal and BMPs, as well as Wnt morphogens.

Ectoderm Wnt1/3

Endoderm BMP2, FGF8, SHh

(cardiogenic inducers) Cerberus

Mesoderm

Notochord Noggin, chordin

Cardiac mesoderm GATA4/5/6, MyoCd, NKx2.5 SRF, TBx20, TH, Wnt11

anterior heart fields that contribute to the left ventricle and right ventricle and
outflow tract, respectively. Unlike the first heart field, second heart field cells remain
undifferentiated until they migrate into the forming heart.
Both heart field cells are tagged by the homeobox NK2 transcription factor-
related locus-5 protein NKx2-5 encoded by homeobox NKX2-5 gene, 2 whereas
transcription factor Islet-1 (Isl1) 3 is only involved in the differentiation of second
heart field cells. Second heart field cells persist in the postnatal heart. These
progenitors can differentiate into several types of cardiac cells. 4

In human fetal

+

hearts at 11 and 18 weeks of gestation, Isl1 cells lodge in the right atrium and

outflow tract that are both second heart field-derived structures as well as left atrial
wall and appendage [ 487 ].

2 The homeobox gene NKX2-5 (or NKX2.5) is also called cardiac-specific homeobox CSx.
The homeobox gene set includes many members (NKX2-1-NKX2-6). Homeodomain protein
NKx2-1 corresponds to thyroid transcription factor-1. It is also expressed in lungs. Factor NKx2-5
is also produced in the primitive pharyngeal endoderm that secretes the heart inducer.
3 Homeobox protein Isl1 as well as Pdx1 of endocrine cells of the gastric mucosa that control the
production of gastrointestinal hormones were discovered in pancreatic islets.
4 Damaged heart components (valves, vessels, nodal conduction tissue, and myocardium) must
be regenerated. The mobilization of endogenous progenitors and differentiation of exogenous
stem cells participate in tissue repair. Adult stem cells are genetically equivalent to embryonic
cells. Differential gene expression results from reversible epigenetic changes gradually imposed
on the genome during development. However, adult cells have a reprogramming capacity toward
an undifferentiated embryonic state, as differentiation is reversible.