Jun NH2-terminal kinase (JNK) prevents nuclear beta-catenin accumulation and regulates axis formation in Xenopus embryos.
Jun NH(2)-terminal kinases (JNKs) regulate convergent extension movements in Xenopus embryos through the noncanonical Wnt/planar cell polarity pathway. In addition, there is a high level of maternal JNK activity spanning from oocyte maturation until the onset of gastrulation that has no defined functions. Here, we show that maternal JNK activation requires Dishevelled and JNK is enriched in the nucleus of Xenopus embryos. Although JNK activity is not required for the glycogen synthase kinase-3-mediated degradation of beta-catenin, inhibition of the maternal JNK signaling by morpholino-antisense oligos causes hyperdorsalization of Xenopus embryos and ectopic expression of the Wnt/beta-catenin target genes. These effects are associated with an increased level of nuclear and nonmembrane-bound beta-catenin. Moreover, ventral injection of the constitutive-active Jnk mRNA blocks beta-catenin-induced axis duplication, and dorsal injection of active Jnk mRNA into Xenopus embryos decreases the dorsal marker gene expression. In mammalian cells, activation of JNK signaling reduces Wnt3A-induced and beta-catenin-mediated gene expression. Furthermore, activation of JNK signaling rapidly induces the nuclear export of beta-catenin. Taken together, these results suggest that JNK antagonizes the canonical Wnt pathway by regulating the nucleocytoplasmic transport of beta-catenin rather than its cytoplasmic stability. Thus, the high level of sustained maternal JNK activity in early Xenopus embryos may provide a timing mechanism for controlling the dorsal axis formation.
Liao
Guanghong
G
Department of Pediatrics, Division of Developmental Biology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Tao
Qinghua
Q
Kofron
Matthew
M
Chen
Juei-Suei
JS
Schloemer
Aryn
A
Davis
Roger J
RJ
Hsieh
Jen-Chih
JC
Wylie
Chris
C
Heasman
Janet
J
Kuan
Chia-Yi
CY
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001368:Axis, Cervical Vertebra / Q000196:embryology / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism*; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009035:Mothers; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D014158:Transcription, Genetic / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism; D014981:Xenopus / Q000196:embryology* / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D051153:Wnt Proteins; D051176:beta Catenin; D048031:JNK Mitogen-Activated Protein Kinases