title: Feedback inhibition of Jak/STAT signaling by apontic is required to limit an invasive cell population.
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.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Starz-Gaiano
authors.forename: Mariana
authors.initials: M
authors.lastname: Melani
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.forename: Hans
authors.initials: H
authors.lastname: Meinhardt
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Montell
mesh_terms: D000483:Alleles; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics; D025461:Feedback, Physiological; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053612:Janus Kinases / Q000378:metabolism*; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050791:STAT Transcription Factors; D014157:Transcription Factors; C108529:apt protein, Drosophila; C077246:slbo protein, Drosophila; D053612:Janus Kinases