A beta-catenin-independent dorsalization pathway activated by Axin/JNK signaling and antagonized by aida.
Axin is a scaffold protein that controls multiple important pathways, including the canonical Wnt pathway and JNK signaling. Here we have identified an Axin-interacting protein, Aida, which blocks Axin-mediated JNK activation by disrupting Axin homodimerization. During investigation of in vivo functions of Axin/JNK signaling and aida in development, it was found that Axin, besides ventralizing activity by facilitating beta-catenin degradation, possesses a dorsalizing activity that is mediated by Axin-induced JNK activation. This dorsalizing activity is repressed when aida is overexpressed in zebrafish embryos. Whereas Aida-MO injection leads to dorsalized embryos, JNK-MO and MKK4-MO can ventralize embryos. The anti-dorsalization activity of aida is conferred by its ability to block Axin-mediated JNK activity. We further demonstrate that dorsoventral patterning regulated by Axin/JNK signaling is independent of maternal or zygotic Wnt signaling. We have thus identified a dorsalization pathway that is exerted by Axin/JNK signaling and its inhibitor Aida during vertebrate embryogenesis.
Rui
Yanning
Y
Key Laboratory of Ministry of Education for Cell Biology, School of Life Sciences, Xiamen University, Fujian 361005, Xiamen, China.
Xu
Zhen
Z
Xiong
Bo
B
Cao
Ying
Y
Lin
Shuyong
S
Zhang
Min
M
Chan
Siu-Chiu
SC
Luo
Wen
W
Han
Ying
Y
Lu
Zailian
Z
Ye
Zhiyun
Z
Zhou
Hai-Meng
HM
Han
Jiahuai
J
Meng
Anming
A
Lin
Sheng-Cai
SC
D000818:Animals; D060466:Axin Protein; D019521:Body Patterning / Q000187:drug effects; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D019281:Dimerization; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
C522596:Aida protein, zebrafish; D060466:Axin Protein; D002352:Carrier Proteins; D016376:Oligonucleotides, Antisense; D012097:Repressor Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D048031:JNK Mitogen-Activated Protein Kinases