title: Cripto-independent Nodal signaling promotes positioning of the A-P axis in the early mouse embryo.
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.
authors.affiliation: IBB-Institute for Biotechnology and Bioengineering, Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, Campus de Gambelas, 8005-135 Faro, Portugal. liguori@igb.cnr.it
authors.forename: Giovanna L
authors.initials: GL
authors.lastname: Liguori
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Borges
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Andrea
authors.forename: Annamaria
authors.initials: A
authors.lastname: Liguoro
authors.forename: Lisa
authors.initials: L
authors.lastname: Gonçalves
authors.forename: Ana Marisa
authors.initials: AM
authors.lastname: Salgueiro
authors.forename: M Graziella
authors.initials: MG
authors.lastname: Persico
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Belo
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000502:physiology; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D016207:Cytokines; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D004815:Epidermal Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005260:Female; D054262:Gastrulation / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D055457:Nodal Protein; D020897:Organizers, Embryonic / Q000502:physiology; D011247:Pregnancy; D011506:Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
chemical_list: C110586:Cer1 protein, mouse; C104433:Cfc1 protein, mouse; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D055457:Nodal Protein; C526008:Nodal protein, mouse; D011506:Proteins; C489450:Tdgf1 protein, mouse; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D030201:Activin Receptors, Type I; C515277:Acvr1c protein, mouse