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Cripto-independent Nodal signaling promotes positioning of the A-P axis in the early mouse embryo.

Liguori GL, Borges AC, D'Andrea D, Liguoro A, Gonçalves L, Salgueiro AM, Persico MG, Belo JA

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

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.

Published 10 March 2008 in Dev Biol, 315(2): 280-9.
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Volume 1 (2005)
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Embryology Books

The Ontogenetic Basis of Human Anatomy: The Biodynamic Approach to Development from Conception to Adulthood

The Ontogenetic Basis of Human Anatomy: The Biodynamic Approach to Development from Conception to Adulthood