Biomedical Engineering Reference
In-Depth Information
from binding to their receptors) prevents myocardial differentiation. In addition,
several members of the BMP family with overlapping functions are expressed in the
cardiac mesoderm, such as BMP5 and BMP7 [
483
].
Hedgehog
Both sonic and indian Hedgehog are expressed in the pharyngeal endoderm during
cardiac crescent formation [
483
]. They operate as permissive rather than inductive
factors via Smoothened receptor during cardiogenesis.
Wnt
Wnt morphogens operate as positive and negative regulators of the primary heart
field. Subtype Wnt1 in the heart field blocks myocardial differentiation and induces
blood formation. Canonical Wnt signals that operate via
-catenin, such as Wnt2a,
Wnt2b, Wnt3, and Wnt8 regulate specification of cardiac cell types from the early
mesoderm [
517
]. On the other hand, Wnt5a and Wnt11 trigger the non-canonical
Wnt pathways during cardiogenesis. Subtype Wnt11 activates, via G protein, PKC,
JNK, and CamK2 kinases.
An alternative branch of the Wnt pathway uses Jun N-terminal kinases for
gastrulation movements. Diversin
20
β
interacts with 2 components of the canonical
Wnt pathway, casein kinase-1
, and axin. It suppresses Wnt signals mediated
by the canonical
-catenin pathway and stimulates signaling via Jun N-terminal
kinases [
518
]. Diversin controls fusion of heart precursors [
519
]. Diversin binds
Disheveled to activate Rac and Rho GTPases and then Jun N-terminal kinase.
Morphogen Wnt11 controls early assembly of ventriculomyocytes, especially
coordinated organization with intercellular contacts that rely on colocalized cell
adhesion components, such as N-cadherin and
β
-catenin [
517
].
21
β
6.1.8.5
Chromatin Remodelers
The large ATP-dependent chromatin-remodeling switching/sucrose non-fermenting
(Swi/SNF)-like BAF (Brahma-related gene [BRG1]/Brahma [Brm]-associated fac-
tor) complex uses the energy of ATP hydrolysis to modify the chromatin structure
made of DNA and histones, thereby activating or repressing gene expression.
20
A.k.a. ankyrin repeat domain-containing protein-6 (AnkRD6).
21
In mice, Wnt11 is synthesized in or in close proximity to the precardiac mesoderm, and later
in the myocardium of the primitive heart tube, thereby overlapping the first and secondary heart
fields. At later stages, Wnt11 as well as Wnt5a are expressed in the outflow tract.
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