Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 282

( L DOPA) 16 that generates dopamine, a catecholamine neurotransmitter and

hormone, by aromatic amino acid decarboxylase.
Catecholamines present during cardiogenesis comprise L DOPA (predominantly)
and dopamine. Molecule L DOPA enhances BMP2 production. It may be an
important modulator of cardiac pacemaker activity, as it leads cardiac precursor
cells to a sinoatrial fate [ 511 ].
Tyrosine hydroxylase regionalizes the production of atrial myosin heavy chain
(aMHC1) and TBx5 factor to the posterior region of the heart tube during initial
cardiomyocyte differentiation [ 511 ]. Retinoic acid synthesis is required for Tyr
hydroxylase activity, hence expression of aMHC1 and TBx5 proteins.

6.1.8.3 Growth Factors

FGF

Fibroblast growth factor-8 (FGF8) that promotes cardiogenesis lodges in the anterior
heart field and a subset of the primary heart field cells [ 512 , 513 ]. Autocrine
signaling launched by FGF8 is required in the anterior heart field to promote cell
proliferation and survival.

Neuregulin-1

Signaling triggered by neuregulin-1, a member of the epidermal growth factor
(EGF) family (Sect. 6.1.5 ), and its heterodimeric receptor protein Tyr kinase HER2-
HER4 participates in cardiogenesis as well as proper structure and function of the
adult heart. 17

16 Molecule L DOPA is a precursor to dopamine, noradrenaline, and adrenaline. Dopamine can be
converted to noradrenaline by dopamine β -hydroxylase and adrenaline in the nervous system and
adrenal glands.
17 Neuregulin-1 carries out diverse functions in different cell types. It operates in the differentiation
of neurons, thereby acting as a neuronal differentiation factor, accumulation of acetylcholine
receptors in skeletal muscle, and proliferation of glial cells, hence serving as a glial growth
factor. Neuregulin-1 is encoded by a single gene (NRG1). It has numerous isoforms produced
by alternative splicing. Isoform-1 (heregulin), -2 (glial growth factor GGF2), and -3 (sensory and
motor neuron-derived factor [SMDF]) are processed as transmembrane proteins that contain EGF-
like domains. Heregulin and glial growth factor GGF2 that possess a heparin-binding domain
(HBD) are cleaved by adamlysins into soluble forms that act as paracrine factors. Sensory and
motor neuron-derived factor is also cleaved by adamlysins; its EGF motif-containing extracellular
domain (SMDF ECD ) remains attached to the transmembrane domain through the cysteine-rich
domain (CRD) to signal as a juxtacrine messengers. Neuregulin-1 acts via receptor protein Tyr
kinases HER2 to HER4.