Negative regulation of wnt11 expression by Jnk signaling during zebrafish gastrulation

Jungwon Seo, Yoichi Asaoka, Yoko Nagai, Jun Hirayama, Tokiwa Yamasaki, Misako Namae, Shinya Ohata, Nao Shimizu, Takahiro Negishi, Daiju Kitagawa, Hisato Kondoh, Makoto Furutani-Seiki, Josef M. Penninger, Toshiaki Katada, Hiroshi Nishina

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


Stress-induced Sapk/Jnk signaling is involved in cell survival and apoptosis. Recent studies have increased our understanding of the physiological roles of Jnk signaling in embryonic development. However, still unclear is the precise function of Jnk 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 Jnk activators Mkk4 and Mkk7 to examine the effect of Jnk 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 Jnk activation via the non-canonical Wnt pathway. Conversely, ectopic activation of Jnk signaling by overexpression of an active form of Mkk4b led to wnt11 downregulation. Mosaic lineage tracing studies revealed that Mkk4b-Jnk 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 Jnk 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 - 2010 Jul 1
Externally publishedYes


  • Convergent extension
  • Gastrulation
  • Jnk
  • Mkk4
  • Wnt11
  • Zebrafish

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Negative regulation of wnt11 expression by Jnk signaling during zebrafish gastrulation'. Together they form a unique fingerprint.

Cite this