Cerberus regulates left–right asymmetry of the embryonic head and heart

Zhu, Lei; Marvin, Martha J.; Gardiner, Aaron; Lassar, Andrew B.; Mercola, Mark; Stern, Claudio D.; Levin, Michael

doi:10.1016/s0960-9822(99)80419-9

Cited by 126 publications

(100 citation statements)

References 43 publications

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“…Consistent with findings in frog and chick embryos Yokouchi et al 1999;Zhu et al 1999), electroporation of caAlk6-tdRed into the left LPM led to local inhibition of Pitx2 expression (weak, localized, or fragmented expression) in most embryos (n = 27/32; 84%), while eGFP vector had no effect (n = 12; P < 0.001) ( Fig. 7H-IЈ; Supplemental Table 1).…”

Section: Smad4 Derepresses Lr Signaling In the Right Lpmsupporting

confidence: 86%

BMP/SMAD1 signaling sets a threshold for the left/right pathway in lateral plate mesoderm and limits availability of SMAD4

Furtado¹,

Solloway²,

Jones³

et al. 2008

Genes Dev.

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The left/right (LR) axial pathway establishes asymmetry in the patterning and morphogenesis of multiple internal organs, including the heart. In mammals, this pathway involves the breaking of molecular symmetry in or around the node, transfer of asymmetry information to the lateral plate mesoderm (LPM), propagation of molecular asymmetries throughout the LPM, and interpretation of these signals for proper organ morphogenesis (Nonaka et al. 2002). Recent experiments have demonstrated that the breaking of bilateral symmetry in the mouse node occurs via a process termed "nodal flow," in which motile cilia in the node generate leftward movement of molecular determinants via lipoprotein vesicles (Hirokawa et al. 2006;. NODAL, a transforming growth factor ␤ (TGF␤) superfamily member, is a key molecule in the LR cascade. NODAL acts first in mesoderm specification and anterior-posterior axis formation, signaling through a membrane complex containing type I and II TGF␤ serine/ threonine kinase receptors, as well as GPI-anchored members of the EGF-CFC family. This complex phosphorylates intracellular SMAD2 and SMAD3, which associate with the common TGF␤/NODAL/BMP (bone morphogenetic protein) pathway SMAD, SMAD4, and forkhead transcription factor FOXH1, to regulate downstream target genes (Shen 2007). In the LR pathway,

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Section: Smad4 Derepresses Lr Signaling In the Right Lpmsupporting

confidence: 86%

BMP/SMAD1 signaling sets a threshold for the left/right pathway in lateral plate mesoderm and limits availability of SMAD4

Furtado¹,

Solloway²,

Jones³

et al. 2008

Genes Dev.

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show abstract

“…Rather, Cerberus-related proteins are key regulators of Nodal signaling and play an important role in the establishment of left -right asymmetry in the vertebrate embryo (Rodriguez Esteban et al 1999;Yokouchi et al 1999;Zhu et al 1999;Hashimoto et al 2004;Marques et al 2004;Tavares et al 2007;Vonica and Brivanlou 2007).…”

Section: Cerberusmentioning

confidence: 99%

Secreted and Transmembrane Wnt Inhibitors and Activators

Cruciat

Niehrs

2012

Cold Spring Harbor Perspectives in Biology

522

450

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“…Cerberus is expressed in the organizer region of Xenopus gastrula stage embryos (Bouwmeester et al 1996) and can serve as an antagonist of Wnt, BMP, and nodal signaling (Glinka et al 1997;Hsu et al 1998;Piccolo et al 1999). Chick cerberus-1/ caronte is expressed in anterior hypoblast and anterior endoderm but is down-regulated in endoderm by stage 4 (Rodriguez Esteban et al 1999;Yokouchi et al 1999;Zhu et al 1999), whereas the heart-inducing capacity of endoderm is retained in this tissue until at least stage 8 − (G. Di Rocco and A.B. Lassar, unpubl.).…”

Section: Other Candidate Heart-inducing Factorsmentioning

confidence: 99%

Inhibition of Wnt activity induces heart formation from posterior mesoderm

Marvin¹,

Rocco²,

Gardiner³

et al. 2001

Genes Dev.

Self Cite

534

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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Cerberus regulates left–right asymmetry of the embryonic head and heart

Abstract: Our findings suggest that cCer maintains a delicate balance of different TGF-beta family members involved in laterality decisions, and reveal the existence of partially overlapping molecular pathways regulating left-right asymmetry in the head and trunk of the embryo.

Cited by 126 publications

References 43 publications

BMP/SMAD1 signaling sets a threshold for the left/right pathway in lateral plate mesoderm and limits availability of SMAD4

BMP/SMAD1 signaling sets a threshold for the left/right pathway in lateral plate mesoderm and limits availability of SMAD4

Secreted and Transmembrane Wnt Inhibitors and Activators

Inhibition of Wnt activity induces heart formation from posterior mesoderm

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