JCB logo
R&D Systems
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online February 11, 2008
doi:10.1083/jcb.200709090
The Journal of Cell Biology, Vol. 180, No. 3, 597-605
The Rockefeller University Press, 0021-9525 $30.00
© 2008 D'Andrea et al.
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by D'Andrea, D.
Right arrow Articles by Minchiotti, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by D'Andrea, D.
Right arrow Articles by Minchiotti, G.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

 Cripto promotes A–P axis specification independently of its stimulatory effect on Nodal autoinduction

Daniela D'Andrea1, Giovanna L. Liguori1, J. Ann Le Good2, Enza Lonardo1, Olov Andersson2, Daniel B. Constam2, Maria G. Persico1, and Gabriella Minchiotti1

1 Stem Cell Fate Laboratory, Institute of Genetics and Biophysics "A. Buzzati-Traverso," Consiglio Nazionale delle Ricerche, 80131 Naples, Italy
2 Federal Institute of Technology Lausanne and Swiss Institute for Experimental Cancer Research, CH 1066 Epalinges, Switzerland

Correspondence to Gabriella Minchiotti: minchiot{at}igb.cnr.it

The EGF-CFC gene cripto governs anterior–posterior (A–P) axis specification in the vertebrate embryo. Existing models suggest that Cripto facilitates binding of Nodal to an ActRII–activin-like kinase (ALK) 4 receptor complex. Cripto also has a crucial function in cellular transformation that is independent of Nodal and ALK4. However, how ALK4-independent Cripto pathways function in vivo has remained unclear. We have generated cripto mutants carrying the amino acid substitution F78A, which blocks the Nodal–ALK4–Smad2 signaling both in embryonic stem cells and cell-based assays. In criptoF78A/F78A mouse embryos, Nodal fails to expand its own expression domain and that of cripto, indicating that F78 is essential in vivo to stimulate Smad-dependent Nodal autoinduction. In sharp contrast to cripto-null mutants, criptoF78A/F78A embryos establish an A–P axis and initiate gastrulation movements. Our findings provide in vivo evidence that Cripto is required in the Nodal–Smad2 pathway to activate an autoinductive feedback loop, whereas it can promote A–P axis formation and initiate gastrulation movements independently of its stimulatory effect on the canonical Nodal–ALK4–Smad2 signaling pathway.

Abbreviations used in this paper: A–P, anterior–posterior; ALK, activin-like kinase; ARE, activin response element; CFC, Cripto-FRL1-Cryptic; dpc, days past coitum; EB, embryoid body; ERK, extracellular signal-regulated kinase; ES, embryonic stem; GDF, growth/differentiation factor; GPI, glycophosphatidylinositol; oep, one-eyed pinhead.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents