Negative regulation of wnt11 expression by Jnk signaling during zebrafish gastrulation

J Seo, Y Asaoka, Y Nagai, J Hirayama, T Yamasaki, M Namae, S Ohata, N Shimizu, T Negishi, D Kitagawa, H Kondoh, Makoto Furutani-Seiki, J M Penninger, T Katada, H Nishina

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26 Citations (SciVal)


Stress-induced Sapk/Jnk signaling is involved in cell survival and apoptosis. Recent studies have increased our understanding of the physiological roles of ink signaling in embryonic development. However, still unclear is the precise function of ink signaling during gastrulation, a critical step in the establishment of the vertebrate body plan. Here we use morpholino-mediated knockdown of the zebrafish orthologs of the ink activators Mkk4 and Mkk7 to examine the effect of ink signaling abrogation on early vertebrate embryogenesis. Depletion of zebrafish Mkk4b led to abnormal convergent extension (CE) during gastrulation, whereas Mkk7 morphants exhibited defective somitogenesis. Surprisingly, Mkk4b morphants displayed marked upregulation of wnt11, which is the triggering ligand of CE and stimulates ink activation via the non-canonical Win pathway. Conversely, ectopic activation of ink signaling by overexpression of an active form of Mkk4b led to wnt11 downregulation. Mosaic lineage tracing studies revealed that Mkk4b-ink signaling suppressed wnt11 expression in a non-cell-autonomous manner. These findings provide the first evidence that wnt11 itself is a downstream target of the Jnk cascade in the non-canonical Wnt pathway. Our work demonstrates that Jnk activation is indispensable for multiple steps during vertebrate body plan formation. Furthermore, non-canonical Wnt signaling may coordinate vertebrate CE movements by triggering ink activation that represses the expression of the CE-triggering ligand wnt11.
Original languageEnglish
Pages (from-to)1022-1037
Number of pages16
JournalJournal of Cellular Biochemistry
Issue number4
Publication statusPublished - 1 Jul 2010


  • JNK
  • convergent extension
  • MKK4
  • WNT11
  • gastrulation
  • zebrafish


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