Antagonistic interaction between IGF and Wnt/JNK signaling in convergent extension in Xenopus embryo.
The homeobox gene Otx2 is expressed during gastrulation in the anterior domain of the vertebrate embryo and is involved in neural and head induction during Xenopus early development. It also prevents convergent extension movements in trunk and posterior mesoderm. Insulin-like growth factors (IGFs) were shown to have similar function. However, whether they interact and the mechanism by which they affect convergent extension remain unclear. We show that IGF pathway specifically induces the expression of Otx2 in the early gastrula and blocks convergent extension of neuroectoderm and mesoderm through the transcriptional activation of Otx2 gene. Otx2 represses the expression of Xbra and Xwnt-11, and the effects of IGF on gastrulation movements can be partially rescued by antisense Otx2 morpholino oligonucleotide. These indicate that IGF pathway interacts with Otx2 to restrict Xbra and Xwnt-11 expression in the trunk and posterior regions. Consistent with this, we show that inhibition of IGF signaling or Otx2 function induces Xbra and Xwnt11 expression and convergent extension in ectodermal cells. Furthermore, the blockade of convergent extension by IGF-I and Otx2 can be rescued by coexpression of Xwnt-11 or a constitutively active Jun N-terminal kinase (JNK). Because Xbra and Xwnt-11 are required for convergent extension movements and Xwnt-11 activates the non-canonical Wnt-11/JNK pathway, our results reveal a mutually exclusive function between IGF and Wnt-11/JNK pathways in regulating cell behaviours during vertebrate head and trunk development.
Carron
Clémence
C
Groupe de Biologie Expérimentale, Laboratoire de Biologie du Développement, CNRS UMR 7622, Université Paris 6, 9 quai Saint-Bernard, 75005 Paris, France.
Bourdelas
Audrey
A
Li
Hong-Yan
HY
Boucaut
Jean-Claude
JC
Shi
De-Li
DL
D000818:Animals; D004625:Embryo, Nonmammalian / Q000502:physiology; D005775:Gastrula / Q000502:physiology; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013002:Somatomedins / Q000037:antagonists & inhibitors*; D020825:T-Box Domain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D014981:Xenopus; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D017405:Herpes Simplex Virus Protein Vmw65; D051857:Otx Transcription Factors; C497661:Otx2 protein, Xenopus; D011993:Recombinant Fusion Proteins; D013002:Somatomedins; D020825:T-Box Domain Proteins; C116765:TBXT protein, Xenopus; D051153:Wnt Proteins; D029867:Xenopus Proteins; C512785:wnt11b protein, Xenopus; D048031:JNK Mitogen-Activated Protein Kinases