Requirement for JAK/STAT signaling throughout border cell migration in Drosophila.
The evolutionarily conserved JAK/STAT signaling pathway is essential for the proliferation, survival and differentiation of many cells including cancer cells. Recent studies have implicated this transcriptional pathway in the process of cell migration in humans, mice, Drosophila and Dictyostelium. In the Drosophila ovary, JAK/STAT signaling is necessary and sufficient for the specification and migration of a group of cells called the border cells; however, it is not clear to what extent the requirement for cell fate is distinct from that for cell migration. We found that STAT protein is enriched in the migrating border cells throughout their migration and is an indicator of cells with highest JAK/STAT activity. In addition, stat(ts) mutants exhibited border cell migration defects after just 30 minutes at the non-permissive temperature, prior to any detectable change in the expression of cell fate markers. At later times, cell fate changes became evident, indicating that border cell fate is labile. JAK/STAT signaling was also required for organization of the border cell cluster. Finally, we show that both the accumulation of STAT protein and nuclear accumulation are positively regulated by JAK/STAT activity. The activity of the pathway is negatively regulated by overexpression of a SOCS protein and by blocking endocytosis. Together, our findings suggest that the requirement for STAT in border cells extends beyond the initial specification and delamination of cells from the epithelium.
Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 212052, USA.
Debra L
DL
Silver
Erika R
ER
Geisbrecht
Denise J
DJ
Montell
D000818:Animals; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000502:physiology; D004705:Endocytosis; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D053612:Janus Kinases; D051379:Mice; D009866:Oogenesis; D010053:Ovary / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D050791:STAT Transcription Factors; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050791:STAT Transcription Factors; C105675:Stat92E protein, Drosophila; D015534:Trans-Activators; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D053612:Janus Kinases; C085845:hop protein, Drosophila