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after transient treatment with conditioned media containing Wnt11
during differentiation [62].
In conclusion, the roles of Wnt signaling in heart development
are as follows: The canonical Wnt pathway is important for either
mesoderm formation or the proliferation of cardiac progenitors.
The canonical Wnt pathway has inhibitory effects on cardiac
specification,whilethenoncanonicalWntpathwaypromotescardiac
differentiation.
2b.4 FGF Signaling in Cardiac Differentiation
FGFsareknowntopromotethegrowthoffibroblasts[63].Moreover,
FGF promotion of growth and differentiation is shared among
various cells. FGFs are also involved in various biological processes
such as morphogenesis, tissue remodeling, and metabolic control.
Morethan20FGFshavebeenidentified,andtheirsignalingis
transduced by four types of receptor tyrosine kinases (Fig. 2b.2). FGF
binding to receptor tyrosine kinases causes activation via receptor
dimerization.Theintracellulardomainofthedimerizedreceptor
is phosphorylated, which contains adaptor molecule-binding sites.
There are primarily three cascades downstream of the FGF signaling
pathway,namely,theRas/MAPK,PLCĪ³/Ca
, and PI3K pathways.
In chick embryos, either alpha-actin expression or formation of the
contractile explant is induced by FGF2 in the precardiac mesoderm
explant [64]. In addition, cardiac precursor proliferation is inhibited
by treatment with either FGF2 antisense oligonucleotides or an
FGFreceptor1(FGFR1)-neutralizingantibody[65,66].Although
endoderm removal from chick embryos results in decreased
expression of cardiac marker genes such as
2+
Nkx2.5
and
Mef2C
, the
reduction is rescued by FGF8 [67]. Furthermore,
Nkx2.5
and
Mef2C
ectopic expression is induced by FGF8 ectopic expression in the
lateralregionofthenormalheartfield.Inmouseembryos,analyses
of FGF8 hypomorphic alleles and conditional FGF8 ablation using
a series of Cre lines revealed that mesodermal FGF8 is required
forsecondheartfield(SHF)developmentandthatFGF8inthe
pharyngealendodermregulatesoutflowtractseparation[68,69].
FGF9,FGF16,andFGF20areexpressedinboththeepicardiumand
the endocardium at midgestation and contribute to myocardial
proliferation and differentiation [70]. This suggests that FGF
