Biomedical Engineering Reference
In-Depth Information
embryos,Wnt6hasbeenconsideredrequiredforspecificationof
the heart region. However, Wnt6 overexpression by a heat shock-
inducible promoter during terminal differentiation stages results in
a decrease in the heart conformation. Conversely, Wnt6 depletion
by antisense morpholino oligo increases cardiac structures [51]. In
mouseembryosatE9.0,severalgenesessentialforcardiacprogeni-
tor cell development, including
diac gene expression and beatingcardiomyocytes[49].In
Xenopus
, have
decreased expression in Isl1+ cardiac progenitors, overexpressing a
beta-catenin-stabilizedvariant[52].
In mouse ES cells, canonical Wnt pathway inhibition has been
considered to promote cardiac differentiation. Previous studies
used Flk1 + CXCR4 + VE-cad cells that have a high capacity for
differentiationintocardiomyocytesincoculturewithOP9cells.
In this coculture system, cardiac differentiation is promoted by
canonical Wnt-signaling inhibition and repressed by Wnt3a [53].
OtherstudiesusedmouseEScell-derivedFlk1+cells,classified
as hemangioblasts, that differentiated into a cardiac lineage by
activating Notch signaling. In this process, canonical Wnt pathway
inhibitors are upregulated by Notch4 activation, which is completely
ablated by Wnt3a [54].
The canonical Wnt pathway has inhibitory roles in terminal
cardiac differentiation. Wnt3a treatment during late phases of
differentiation inhibit cardiac differentiation [44, 45]. In addition,
insulin-like growth factor-binding protein 4 (IGFBP4) acts as a
novel extracellular inhibitory factor of the canonical Wnt pathway. In
Xenopus
Isl1
,
myocardin
,
shh
, and
Smyd1
,IGFBP4interactswithFrz8andLrp6,whichinhibitsWnt3a
binding. In mouse ES cells, IGFBP4 treatment during late phases of
differentiation enhances cardiac differentiation [55].
The noncanonical Wnt pathway is also considered as contributing
to cardiac differentiation in the mesoderm. In
, loss- and gain-
of-function experiments have shown that Wnt11 is required for heart
formation and cardiac marker gene expression [56]. Wnt11-induced
cardiac differentiation has been reported in the quail mesoderm,
endothelial progenitors, and bone marrow-derived cells [57-60].
These results suggest that Wnt11-induced cardiac differentiation is
mediated by JNK or protein kinase C (PKC) signaling pathways [56,
60, 61]. In mouse ES cells, cardiac marker gene expression increases
Xenopus
