Mutation of smooth muscle myosin causes epithelial invasion and cystic expansion of the zebrafish intestine

Kenneth N. Wallace, Amy C. Dolan, Christoph Seiler, Erin M. Smith, Shamila Yusuff, Linda Chaille-Arnold, Ben Judson, Rachel Sierk, Christopher Yengo, H. Lee Sweeney, Michael Pack

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Zebrafish meltdown (mlt) mutants develop cystic expansion of the posterior intestine as a result of stromal invasion of nontransformed epithelial cells. Positional cloning identified zebrafish smooth muscle myosin heavy chain (myh11) as the responsible gene. The mlt mutation constitutively activates the Myh11 ATPase, which disrupts smooth muscle cells surrounding the posterior intestine. Adjacent epithelial cells ectopically express metalloproteinases, integrins, and other genes implicated in human cancer cell invasion. Knockdown and pharmacological inhibition of these genes restores intestinal structure in mlt mutants despite persistent smooth muscle defects. These data identify an essential role for smooth muscle signaling in the maintenance of epithelial architecture and support gene expression analyses and other studies that identify a role for stromal genes in cancer cell invasion. Furthermore, they suggest that high-throughput screens to identify regulators of cancer cell invasion may be feasible in zebrafish.

Original languageEnglish (US)
Pages (from-to)717-726
Number of pages10
JournalDevelopmental Cell
Volume8
Issue number5
DOIs
StatePublished - May 2005

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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