Title | miRNA-mediated feedback inhibition of JAK/STAT morphogen signalling establishes a cell fate threshold. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Yoon WHee, Meinhardt H, Montell DJ |
Journal | Nat Cell Biol |
Volume | 13 |
Issue | 9 |
Pagination | 1062-9 |
Date Published | 2011 Aug 21 |
ISSN | 1476-4679 |
Keywords | Algorithms, Animals, Animals, Genetically Modified, Cell Line, DNA-Binding Proteins, Drosophila melanogaster, Drosophila Proteins, Feedback, Physiological, Female, Green Fluorescent Proteins, Immunohistochemistry, Janus Kinases, Male, MicroRNAs, Microscopy, Confocal, Models, Biological, Mutation, Oocytes, Ovary, STAT Transcription Factors, Transcription Factors |
Abstract | <p>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.</p> |
DOI | 10.1038/ncb2316 |
Alternate Journal | Nat Cell Biol |
PubMed ID | 21857668 |
PubMed Central ID | PMC3167036 |
Grant List | R01 GM046425 / GM / NIGMS NIH HHS / United States R01 GM046425-10S1 / GM / NIGMS NIH HHS / United States GM46425 / GM / NIGMS NIH HHS / United States |