Abstract
During early mouse development, the TGFbeta-related protein Nodal specifies the organizing centers that control the formation of the anterior-posterior (A-P) axis. EGF-CFC proteins are important components of the Nodal signaling pathway, most likely by acting as Nodal coreceptors. However, the extent to which Nodal activity depends on EGF-CFC proteins is still debated. Cripto is the earliest EGF-CFC gene expressed during mouse embryogenesis and is involved in both A-P axis orientation and mesoderm formation. To investigate the relation between Cripto and Nodal in the early mouse embryo, we removed the Nodal antagonist Cerberus 1 (Cer1) and simultaneously Cripto, by generating Cer1;Cripto double mouse mutants. We observed that two thirds of the Cer1;Cripto double mutants are rescued in processes that are severely compromised in Cripto(-/-) embryos, namely A-P axis orientation, anterior mesendoderm and posterior neuroectoderm formation. The observed rescue is strongly reduced in Cer1;Cripto;Nodal triple mutants, suggesting that Nodal can signal extensively in the absence of Cripto, if Cer1 is also inhibited. This signaling activity drives A-P axis positioning. Our results provide evidence for the existence of Cripto-independent signaling mechanisms, by which Nodal controls axis specification in the early mouse embryo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activin Receptors, Type I / genetics
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Activin Receptors, Type I / physiology
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Animals
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Body Patterning / genetics
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Body Patterning / physiology*
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Cytokines
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Embryonic Development / genetics
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Embryonic Development / physiology
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Epidermal Growth Factor / deficiency
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Epidermal Growth Factor / genetics
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Epidermal Growth Factor / physiology*
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Female
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Gastrulation / genetics
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Gastrulation / physiology
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Gene Expression Profiling
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Gene Expression Regulation, Developmental
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In Situ Hybridization
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / physiology
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neoplasm Proteins / deficiency
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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Nodal Protein
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Organizers, Embryonic / physiology
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Pregnancy
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Proteins / genetics
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Proteins / physiology
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Signal Transduction / genetics
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Signal Transduction / physiology
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / physiology*
Substances
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Cer1 protein, mouse
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Cfc1 protein, mouse
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Cytokines
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Intercellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Neoplasm Proteins
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Nodal Protein
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Nodal protein, mouse
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Proteins
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Tdgf1 protein, mouse
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Transforming Growth Factor beta
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Epidermal Growth Factor
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Activin Receptors, Type I
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Acvr1c protein, mouse