Biomedical Engineering Reference
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after birth. In cardiomyocytes, expression of E2F4 declines during embryogenesis.
Cardiomyocyte hypertrophy then occurs. Reinduction of proliferation of postnatal
cardiomyocytes relies on E2F4 production.
Transcriptional Control of Chamber Formation
Two Hairy enhancer of Split (HES)-related transcription repressors — HRT1 and
HRT2 — are produced in atrial and ventricular progenitor cells [
483
]. They are
controlled by the Notch signaling pathway.
Iroquois-related homeobox protein Irx4 labels ventricular progenitor cells in
the cardiac crescent. Once chambers are formed, Irx4 is exclusively expressed in
ventricles [
483
].
The transcription factors, heart and neural crest derivatives expressed proteins
HAND1 and HAND2 (or bHLHa27 and bHLHa26, respectively) are also involved
in ventricle formation. Both factors are coexpressed in the primary heart tube.
Afterward, bHLHa26 and bHLHa27 accumulate in the right and left ventricle,
respectively [
483
].
Myocyte enhancer factor-2C, which is phosphorylated by P38MAPK
α
and
ERK4 (or ERK5) kinases, is needed for right ventricle construction.
On the other hand, the atrial myocardium is stamped by GATA4 and TBx5
factors.
14
Nuclear receptor NR2f1 is restricted to the inflow tract myocardium [
483
].
The allocation of cells to the atrial and ventricular lineages is also regulated
by retinoic acid. Retinoic acid-synthesizing enzyme retinaldehyde dehydrogenase
RAlDH2 is specifically synthesized in the posterior heart region, where retinoic
acid participates in the formation of atria [
483
].
Specialized regions that demarcate the future working myocardium of atria and
ventricles produce connexin-40 and -43, atrial natriuretic peptide, and X-linked
small muscular protein
15
(SMPX) [
483
].
6.1.8.2
Tyrosine Hydroxylase
Tyrosine hydroxylase, ot tyrosine 3-monooxygenase, the rate-limiting enzyme in
catecholamine synthesis, is strongly produced in the cardiac mesoderm. Tyrosine
hydroxylase catalyzes the conversion of
L
tyrosine to
L
(3,4)-dihydroxyphenylalanine
14
Shortly after early heart formation, GATA4 is downregulated in the anterior part of the heart
field.
15
A.k.a. stretch-responsive skeletal muscle protein and Chisel in mice.
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