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Vol. 15, No. 3, pp. 304-315, February 1, 2001
Department of Cell Biology, Harvard Medical School, Boston,
Massachusetts 02115, USA
Heart induction in Xenopus occurs in paired regions of the
dorsoanterior mesoderm in response to signals from the Spemann organizer and underlying dorsoanterior endoderm. These tissues together
are sufficient to induce heart formation in noncardiogenic ventral
marginal zone mesoderm. Similarly, in avians the underlying definitive
endoderm induces cardiogenesis in precardiac mesoderm. Heart-inducing
factors in amphibians are not known, and although certain BMPs and FGFs
can mimic aspects of cardiogenesis in avians, neither can induce the
full range of activities elicited by the inducing tissues. Here we
report that the Wnt antagonists Dkk-1 and Crescent can induce heart
formation in explants of ventral marginal zone mesoderm. Other Wnt
antagonists, including the frizzled domain-containing proteins Frzb and
Szl, lacked this activity. Unlike Wnt antagonism, inhibition of BMP
signaling did not promote cardiogenesis. Ectopic expression of
GSK3
, which inhibits -catenin-mediated Wnt signaling, also
induced cardiogenesis in ventral mesoderm. Analysis of Wnt proteins
expressed during gastrulation revealed that Wnt3A and Wnt8, but not
Wnt5A or Wnt11, inhibited endogenous heart induction. These results
indicate that diffusion of Dkk-1 and Crescent from the organizer
initiate cardiogenesis in adjacent mesoderm by establishing a zone of
low Wnt3A and Wnt8 activity.
[Key Words: Dkk1; Wnt; heart induction; cardiogenesis; dorsal mesoderm]
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