| First Author | D'Andrea D | Year | 2008 |
| Journal | J Cell Biol | Volume | 180 |
| Issue | 3 | Pages | 597-605 |
| PubMed ID | 18268105 | Mgi Jnum | J:186907 |
| Mgi Id | MGI:5433483 | Doi | 10.1083/jcb.200709090 |
| Citation | D'Andrea D, et al. (2008) Cripto promotes A-P axis specification independently of its stimulatory effect on Nodal autoinduction. J Cell Biol 180(3):597-605 |
| abstractText | 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 cripto(F78A/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, cripto(F78A/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. |
