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 language | English (US) |
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Pages (from-to) | 1062-1071 |
Number of pages | 10 |
Journal | Nature cell biology |
Volume | 13 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2011 |
Externally published | Yes |
ASJC Scopus subject areas
- Cell Biology