MiRNA-mediated feedback inhibition of JAK/STAT morphogen signalling establishes a cell fate threshold

Wan Hee Yoon, Hans Meinhardt, Denise J. Montell

Research output: Contribution to journalArticle

Abstract

Patterns of cell fates generated by morphogens are critically important for normal development; however, the mechanisms by which graded morphogen signals are converted into all-or-none cell fate responses are incompletely understood. In the Drosophila ovary, high and sustained levels of the secreted morphogen Unpaired (Upd) specify the migratory border-cell population by activating the signal transducer and activator of transcription (STAT). A lower or transient level of STAT activity specifies a non-migratory population of follicle cells. Here we identify miR-279 as a component of a feedback pathway that further dampens the response in cells with low levels of JAK/STAT activity. miR-279 directly repressed STAT, and loss of miR-279 mimicked STAT gain-of-function or loss of Apontic (Apt), a known feedback inhibitor of STAT. Apt was essential for miR-279 expression in non-migratory follicle cells, whereas another STAT target, Ken and Barbie (Ken), downregulated miR-279 in border cells. Mathematical modelling and simulations of this regulatory circuit including miR-279, Apt and Ken supported key roles for miR-279 and Apt in generating threshold responses to the Upd gradient.

Original languageEnglish (US)
Pages (from-to)1062-1071
Number of pages10
JournalNature Cell Biology
Volume13
Issue number9
DOIs
StatePublished - Sep 2011

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Transducers
Population
Drosophila
Ovary
Down-Regulation

ASJC Scopus subject areas

  • Cell Biology

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MiRNA-mediated feedback inhibition of JAK/STAT morphogen signalling establishes a cell fate threshold. / Yoon, Wan Hee; Meinhardt, Hans; Montell, Denise J.

In: Nature Cell Biology, Vol. 13, No. 9, 09.2011, p. 1062-1071.

Research output: Contribution to journalArticle

Yoon, Wan Hee ; Meinhardt, Hans ; Montell, Denise J. / MiRNA-mediated feedback inhibition of JAK/STAT morphogen signalling establishes a cell fate threshold. In: Nature Cell Biology. 2011 ; Vol. 13, No. 9. pp. 1062-1071.
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