Tousled-like kinase regulates cytokine-mediated communication between cooperating cell types during collective border cell migration.
Collective cell migration is emerging as a major contributor to normal development and disease. Collective movement of border cells in the Drosophila ovary requires cooperation between two distinct cell types: four to six migratory cells surrounding two immotile cells called polar cells. Polar cells secrete a cytokine, Unpaired (Upd), which activates JAK/STAT signaling in neighboring cells, stimulating their motility. Without Upd, migration fails, causing sterility. Ectopic Upd expression is sufficient to stimulate motility in otherwise immobile cells. Thus regulation of Upd is key. Here we report a limited RNAi screen for nuclear proteins required for border cell migration, which revealed that the gene encoding Tousled-like kinase (Tlk) is required in polar cells for Upd expression without affecting polar cell fate. In the absence of Tlk, fewer border cells are recruited and motility is impaired, similar to inhibition of JAK/STAT signaling. We further show that Tlk in polar cells is required for JAK/STAT activation in border cells. Genetic interactions further confirmed Tlk as a new regulator of Upd/JAK/STAT signaling. These findings shed light on the molecular mechanisms regulating the cooperation of motile and nonmotile cells during collective invasion, a phenomenon that may also drive metastatic cancer.
Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, CA 93106 Joint International Research Laboratory of Metabolic and Developmental Sciences, Shanghai Jiao Tong University-University of Adelaide Joint Centre for Agriculture and Health, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Wenjuan
W
Xiang
Joint International Research Laboratory of Metabolic and Developmental Sciences, Shanghai Jiao Tong University-University of Adelaide Joint Centre for Agriculture and Health, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Dabing
D
Zhang
Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, CA 93106 denise.montell@lifesci.ucsb.edu.
Denise J
DJ
Montell
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D008297:Male; D010053:Ovary / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D059705:Polar Bodies / Q000166:cytology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050791:STAT Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; C115570:upd1 protein, Drosophila; C498930:tlk protein, Drosophila; D017346:Protein Serine-Threonine Kinases