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XB-ART-40529
PLoS One October 28, 2009; 4 (10): e7650.

Early activation of FGF and nodal pathways mediates cardiac specification independently of Wnt/beta-catenin signaling.

Samuel LJ , Latinkić BV .


Abstract
BACKGROUND: Cardiac induction, the first step in heart development in vertebrate embryos, is thought to be initiated by anterior endoderm during gastrulation, but what the signals are and how they act is unknown. Several signaling pathways, including FGF, Nodal, BMP and Wnt have been implicated in cardiac specification, in both gain- and loss-of-function experiments. However, as these pathways regulate germ layer formation and patterning, their specific roles in cardiac induction have been difficult to define. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the mechanisms of cardiac induction directly we devised an assay based on conjugates of anterior endoderm from early gastrula stage Xenopus embryos as the inducing tissue and pluripotent ectodermal explants as the responding tissue. We show that the anterior endoderm produces a specific signal, as skeletal muscle is not induced. Cardiac inducing signal needs up to two hours of interaction with the responding tissue to produce an effect. While we found that the BMP pathway was not necessary, our results demonstrate that the FGF and Nodal pathways are essential for cardiogenesis. They were required only during the first hour of cardiogenesis, while sustained activation of ERK was required for at least four hours. Our results also show that transient early activation of the Wnt/beta-catenin pathway has no effect on cardiogenesis, while later activation of the pathway antagonizes cardiac differentiation. CONCLUSIONS/SIGNIFICANCE: We have described an assay for investigating the mechanisms of cardiac induction by anterior endoderm. The assay was used to provide evidence for a direct, early and transient requirement of FGF and Nodal pathways. In addition, we demonstrate that Wnt/beta-catenin pathway plays no direct role in vertebrate cardiac specification, but needs to be suppressed just prior to differentiation.

PubMed ID: 19862329
PMC ID: PMC2763344
Article link: PLoS One

Genes referenced: a2m acta2 actl6a acvr1 aplnr cer1 chrd.1 dkk1 eomes fgfr1 gsc hhex irx4 mapk1 mespb mixer mlc1 myf5 myl2 myl3 myod1 nkx2-5 nodal nodal1 nodal3.1 nodal3.2 post sia1 sox17a sox17b.2 tal1 tbx18 tbx5 tbxt tcf3 tnni1 tnni3 tubb2b ventx2.2 wnt8a xpo1


Article Images: [+] show captions
References [+] :
Agius, Endodermal Nodal-related signals and mesoderm induction in Xenopus. 2000, Pubmed, Xenbase


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