Involvement of NLK and Sox11 in neural induction in Xenopus development.
BACKGROUND
The Wnt signal transduction pathway regulates various aspects of embryonal development and has been implicated in promoting cancer. Signalling by Wnts leads to the stabilization of cytosolic beta-catenin, which then associates with TCF transcription factors to regulate expression of Wnt-target genes. The Wnt pathway is further subject to cross-regulation at various levels by other components.


RESULTS
Recent evidence suggests that a specific MAP kinase pathway involving the MAP kinase kinase kinase TAK1 and the MAP kinase NLK counteract Wnt signalling. In particular, it has been shown that TAK1 activates NLK, which phosphorylates TCFs bound to beta-catenin. This phosphorylation down-regulates the DNA-binding activity of a TCF-4/beta-catenin complex, and blocks activation of their target genes. To investigate the role of NLK in Xenopus development, we isolated xNLK, a Xenopus homologue of NLK. Our findings indicate that xNLK is expressed in neural tissues and induces the anterior-neural marker gene, Otx-2. Moreover, xSox11, which is induced by the expression of Chordin, co-operates with xNLK to induce neural development. These molecules also interact in mammalian cells, and expression of a mutant of xNLK lacking kinase activity was found to suppress the induction of neural marker gene expression by xSox11.


CONCLUSIONS
Our findings indicate that xNLK may play a role in neural development together with xSox11 during early Xenopus embryogenesis.
Hyodo-Miura
Junko
J
Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.
Urushiyama
Seiichi
S
Nagai
Shin-ichi
S
Nishita
Michiru
M
Ueno
Naoto
N
Shibuya
Hiroshi
H
D000818:Animals; D002454:Cell Differentiation; D003001:Cloning, Molecular; D004627:Embryonic Induction; D006609:High Mobility Group Proteins / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009420:Nervous System / Q000196:embryology*; D009474:Neurons / Q000166:cytology; D009865:Oocytes; D011485:Protein Binding; D012333:RNA, Messenger; D055751:SOXC Transcription Factors; D014981:Xenopus; D029867:Xenopus Proteins
D006609:High Mobility Group Proteins; D012333:RNA, Messenger; D055751:SOXC Transcription Factors; C490792:Sox11 protein, Xenopus; D029867:Xenopus Proteins; D020928:Mitogen-Activated Protein Kinases; C462720:nemo like kinase, Xenopus