Public Release: 

Where does my heart beat now?

Cold Spring Harbor Laboratory

As published in the February 1st issue of Genes & Development, scientists from Harvard Medical School have greatly expanded our knowledge of embryonic heart development. In a series of three articles, research teams led by Drs. Andrew Lassar and Mark Mercola report on their identification of a crucial regulator of vertebrate heart formation.

The heart is formed from cells originating from the mesoderm, one of the three basic embryonic tissue types. Since the 1960's it has been known that the adjacent endoderm secretes factors that promote heart formation, while the neural tube releases a factor that inhibits heart formation. These factors act as morphogens; they are proteins that specify cell fate in a concentration-dependent manner. The interplay of these morphogens determines the position of the heart.

While bone morphogenetic hormones (BMPs) had previously been identified as agonistic morphogens, the inhibitory morphogen has, until now, remained a mystery. All three research teams have demonstrated that Wnt, one of several mammalian proteins in a family related to a Drosophila morphogen, is this long-sought inhibitory factor. One of the research groups from Dr. Lassar's laboratory has determined that Wnt is the signal secreted by the neural tube that blocks cardiogenesis in the adjacent mesoderm of chick embryos. The other group from Dr. Lassar's lab found that the gradient of Wnt activity along the anterior-posterior embryonic axis inhibits cardiogenesis in non-cardiac regions. The research team led by Dr. Mercola similarly found that Wnt antagonists initiate cardiogenesis in the frog Xenopus.

Taken together, these three studies effectively demonstrate that the Wnt pathway serves as an inhibitor of heart formation in vertebrates. To answer the question posed in the headline by Celion Dion, the vertebrate heart will beat in a position defined by low concentrations of Wnt activity and high concentrations of both Wnt inhibitors and BMP. These results unravel a surprisingly elegant mechanism of heart formation

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