BMP2 is required for early heart development during a distinct time period

Schlange, Thomas; Andrée, Birgit; Arnold, Hans-Henning; Brand, Thomas

doi:10.1016/s0925-4773(99)00311-1

Cited by 192 publications

(173 citation statements)

References 54 publications

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“…In situ hybridization data in the developing chick, frog, and/or mouse has shown that BMP2, BMP4, FGF4, FGF8, WNT11, Dkk1, and crescent are expressed at the right time and place to act as primary stimulators of heart formation in the developing embryo (Kispert et al, 1996;Schultheiss et al, 1997;Shibata et al, 2000;Niehrs et al, 2001;Alsan and Schultheiss, 2002). Moreover, specific inhibition of the expression and/or activity of WNT11 or BMP can significantly diminish the formation of cardiac tissue in the vertebrate embryo (Schultheiss et al, 1997;Schlange et al, 2000;Pandur et al, 2002).…”

Section: Specification Of Precardiac Mesoderm Cellsmentioning

confidence: 99%

Stem cells and the formation of the myocardium in the vertebrate embryo

2003

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A major goal in cardiovascular biology is to repair diseased or damaged hearts with newly generated myocardial tissue. Stem cells offer a potential source of replacement myocytes for restoring cardiac function. Yet little is known about the nature of the cells that are able to generate myocardium and the conditions they require to form heart tissue. A source of information that may be pertinent to addressing these issues is the study of how the myocardium arises from progenitor cells in the early vertebrate embryo. Accordingly, this review will examine the initial events of cardiac developmental biology for insights into the identity and characteristics of the stem cells that can be used to generate myocardial tissue for therapeutic purposes. Anat Rec Part A 276A:2-12, 2004.

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Section: Specification Of Precardiac Mesoderm Cellsmentioning

confidence: 99%

Stem cells and the formation of the myocardium in the vertebrate embryo

2003

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“…The BMP antagonist noggin blocks cardiogenesis in explants of stage 4 precardiac mesoendoderm and blocks cardiogenesis in vivo when ectopically expressed through stage 7 Schlange et al 2000). Conversely, anterior paraxial mesoderm, which lies medial to the heart-forming region and normally gives rise to head mesenchyme, can be induced to express cardiac genes and to form beating cardiac myocytes in explant culture by exposure to BMP-2 at stages 5-6 Andreé et al 1998).…”

mentioning

confidence: 99%

“…Conversely, anterior paraxial mesoderm, which lies medial to the heart-forming region and normally gives rise to head mesenchyme, can be induced to express cardiac genes and to form beating cardiac myocytes in explant culture by exposure to BMP-2 at stages 5-6 Andreé et al 1998). In vivo, implantation of a BMP-2-soaked bead into the anterior paraxial mesoderm induces the expression of Nkx-2.5 and GATA-4 Schlange et al 2000). While BMP signals can induce robust cardiac differentiation from an-terior gastrula stage mesendoderm, posterior mesoderm fails to activate heart markers in response to BMP signals .…”

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confidence: 99%

Inhibition of Wnt activity induces heart formation from posterior mesoderm

Marvin¹,

Rocco²,

Gardiner³

et al. 2001

Genes Dev.

541

459

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In the chick, heart mesoderm is induced by signals from the anterior endoderm. Although BMP-2 is expressed in the anterior endoderm, BMP activity is necessary but not sufficient for heart formation. Previous work from our lab has suggested that one or more additional factors from anterior endoderm are required. Crescent is a Frizzled-related protein that inhibits Wnt-8c and is expressed in anterior endoderm during gastrulation. At the same stages, expression of Wnt-3a and Wnt-8c is restricted to the primitive streak and posterior lateral plate, and is absent from the anterior region where crescent is expressed. Posterior lateral plate mesoderm normally forms blood, but coculture of this tissue with anterior endoderm or infection with RCAS-crescent induces formation of beating heart muscle and represses formation of blood. Dkk-1, a Wnt inhibitor of a different protein family, similarly induces heart-specific gene expression in posterior lateral plate mesoderm. Furthermore, we have found that ectopic Wnt signals can repress heart formation from anterior mesoderm in vitro and in vivo and that forced expression of either Wnt-3a or Wnt-8c can promote development of primitive erythrocytes from the precardiac region. We conclude that inhibition of Wnt signaling promotes heart formation in the anterior lateral mesoderm, whereas active Wnt signaling in the posterior lateral mesoderm promotes blood development. We propose a model in which two orthogonal gradients, one of Wnt activity along the anterior-posterior axis and the other of BMP signals along the dorsal-ventral axis, intersect in the heart-forming region to induce cardiogenesis in a region of high BMP and low Wnt activity.

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“…Members of the bone morphogenetic protein (BMP) family are expressed adjacent to the heart-forming region in avians, and ectopic expression of the BMP antagonist noggin in chick precardiac mesoderm inhibits cardiogenesis (Schultheiss et al 1997;Schlange et al 2000). Conversely, application of BMP2 or BMP4 to chick anterior mesoderm located medial to the heart forming region induces ectopic cardiogenesis (Schultheiss et al 1997;Andree et al 1998).…”

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confidence: 99%

Wnt antagonism initiates cardiogenesis in Xenopus laevis

Schneider¹,

Mercola²

2001

Genes Dev.

458

393

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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.

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BMP2 is required for early heart development during a distinct time period

Cited by 192 publications

References 54 publications

Stem cells and the formation of the myocardium in the vertebrate embryo

Stem cells and the formation of the myocardium in the vertebrate embryo

Inhibition of Wnt activity induces heart formation from posterior mesoderm

Wnt antagonism initiates cardiogenesis in Xenopus laevis

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