Feedback Inhibition of JAK/STAT Signaling by Apontic Is Required to Limit an Invasive Cell Population

Michelle Starz-Gaiano, Mariana Melani, Xiaobo Wang, Hans Meinhardt, Denise J. Montell

Research output: Contribution to journalArticlepeer-review

Abstract

In both normal development and in a variety of pathological conditions, epithelial cells can acquire migratory and invasive properties. Border cells in the Drosophila ovary provide a genetically tractable model for elucidating the mechanisms controlling such behaviors. Here we report the identification of a mutant, apontic (apt), in which the migratory population expanded and separation from the epithelium was impeded. This phenotype resembled gain-of-function of JAK/STAT activity. Gain-of-function of APT also mimicked loss of function of STAT and its key downstream target, SLBO. APT expression was induced by STAT, which bound directly to sites in the apt gene. The data suggest that a regulatory circuit between STAT, APT, and SLBO functions to convert an initially graded signal into an all-or-nothing activation of JAK/STAT and thus to proper cell specification and migration. These findings are supported by a mathematical model, which accurately simulates wild-type and mutant phenotypes.

Original languageEnglish (US)
Pages (from-to)726-738
Number of pages13
JournalDevelopmental Cell
Volume14
Issue number5
DOIs
StatePublished - May 13 2008

Keywords

  • DEVBIO
  • SIGNALING

ASJC Scopus subject areas

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

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