Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 275

bHLHa26 (or HAND2), bHLHa27 (or HAND1), GATA4, ZFPM2, 6 and SRF; (2) in
the proepicardial organ, on retinoid X receptor RXR (or NR2b1) and Wilms tumor

suppressor WT1; (3) in the endothelium, on ephrin-B2, endothelial receptor TIE2,
MAPK7 kinase, PTen phosphatase, neurofibromin NF1, and caspase-8; and (4) in
neural crest cells, on BMPR1a and Paired box Pax3 protein.

α

6.1.5 Neurogenesis

The autonomic nervous system involved in the body's homeostasis and stress
defense includes not only the sympathetic and parasympathetic neurons and their
centers in the central nervous system, but also adrenal medulla. The sympatheti-
coadrenal lineage corresponds to a common progenitor of adrenergic sympathetic
neurons and medullary cells of the adrenal gland. Progenitors of sympathetic ganglia
originate from neural crest cells, which constitute an embryonic progenitor cell
population emigrating from the dorsal aspect of the neural tube. Neural crest cells
generate sympathetic and medullary cell lineages during embryogenesis. The dorsal
aorta acts as a morphogenetic center that coordinates migration and segregation of
neural crest cells [ 494 ]. Bone morphogenetic proteins produced by the dorsal aorta
stimulate the production of CXCL12 chemokine and neuregulin-1 7 (Sect. 6.1.8.3 )in
the para-aortic region. These molecules are chemoattractants. Later, BMP signaling
instructs sympatheticoadrenal specifications.
Cardiac sympathetic noradrenergic neurons need nerve growth factor for survival
and development. Neurturin (Nrtn), a member of the family of glial cell line-derived
neurotrophic factors (GDNF), is required for cardiac parasympathetic cholinergic
neurons [ 495 ]. This neurotrophic factor controls neuron survival and differentiation.
However, because a certain fraction of the population of cardiac cholinergic neu-
rons persists in the absence of neurturin, additional neurotrophic factors intervene.
Members of the GDNF family target their cognate coreceptors (GDNFR

α

1-

α

GDNFR 4) coupled to transmembrane receptor protein Tyr kinase Rearranged

during transfection (ReT; Vol. 3 - Chap. 8. Receptor Kinases). 8 The neurturin

6 Alias ZFPM stands for zinc finger protein multitype. A.k.a. zinc finger protein ZnF89b and Friend
of GATA protein-2 (FOG2).
7 Neuregulin-1 is involved in the development of the nervous system and heart. It acts via receptors
of the HER set. It has numerous isoforms produced by alternative splicing. Isoform NRg1 type-
1 (heregulin), -2 (glial growth factor GGF2), and -3 (sensory and motor neuron-derived factor
[SMDF]) are synthesized in excitatory and inhibitory neurons and astrocytes. Neuregulin-1 is a
cardioactive growth factor released by endothelial cells that ensures cardiac development as well as
structural maintenance and functional integrity. Effectors of the NRg1-HER axis include cardiac-
specific myosin light chain kinase (cMLCK), protein phosphatase-1 (PP1), sarcoplasmic reticulum
Ca 2 + ATPase SERCA2, and focal adhesion kinase (FAK).
8 Glial cell-derived neurotrophic factor and neurturin preferentially bind to GFR

α α

1andGFR 2,

respectively.