Pleiotropy of the Drosophila JAK pathway cytokine Unpaired 3 in development and aging

Liqun Wang, Travis R. Sexton, Claire Venard, Michelle Giedt, Qian Guo, Qian Chen, Douglas A. Harrison

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The Janus kinase (JAK) pathway is an essential, highly re-utilized developmental signaling cascade found in most metazoans. In vertebrates, the JAK intracellular cascade mediates signaling by dozens of cytokines and growth factors. In Drosophila, the Unpaired (Upd) family, encoded by three tandemly duplicated genes, is the only class of ligands associated with JAK stimulation. Unpaired has a central role in activation of JAK for most pathway functions, while Unpaired 2 regulates body size through insulin signaling. We show here that the third member of the family, unpaired 3 (. upd3), overlaps upd in expression in some tissues and is essential for a subset of JAK-mediated developmental functions. First, consistent with the known requirements of JAK signaling in gametogenesis, we find that mutants of upd3 show an age-dependent impairment of fertility in both sexes. In oogenesis, graded JAK activity stimulated by Upd specifies the fates of the somatic follicle cells. As upd3 mutant females age, defects arise that can be attributed to perturbations of the terminal follicle cells, which require the highest levels of JAK activation. Therefore, in oogenesis, the activities of Upd and Upd3 both appear to quantitatively contribute to specification of those follicle cell fates. Furthermore, the sensitization of upd3 mutants to age-related decline in fertility can be used to investigate reproductive senescence. Second, loss of Upd3 during imaginal development results in defects of adult structures, including reduced eye size and abnormal wing and haltere posture. The outstretched wing and small eye phenotypes resemble classical alleles referred to as outstretched (. os) mutations that have been previously ascribed to upd. However, we show that os alleles affect expression of both upd and upd3 and map to untranscribed regions, suggesting that they disrupt regulatory elements shared by both genes. Thus the upd region serves as a genetically tractable model for coordinate regulation of tandemly duplicated gene families that are commonly found in higher eukaryotes.

Original languageEnglish
Pages (from-to)218-231
Number of pages14
JournalDevelopmental Biology
Issue number2
StatePublished - Nov 15 2014

Bibliographical note

Funding Information:
We thank the Bloomington Drosophila Stock Center (supported by NIH P40OD018537), Exelixis Collection at the Harvard Medical School, the Drosophila Genome Resource Center, the Developmental Studies Hybridoma Bank, Joe Duffy, Shubha Govind, Herve Agaisse, Denise Montell, and David Schneider for reagents, Norm Bird for assistance with statistics, and Shubha Govind and Martin Zeidler for sharing unpublished results. We also thank Betty Bett, Richard Cooks, and Esther Dansby for technical assistance through the KBRIN/INBRE Summer Research Program (NCRR P20 RR-16481). This work was supported by the National Science Foundation ( IOS-0318776 and IOS-0920432 to D.A.H.) and the Gertrude Flora Ribble Trust (L.W. and T.R.S.).

Publisher Copyright:
© 2014 Elsevier Inc.


  • Cell signaling
  • Complementation
  • Drosophila
  • Eye development
  • Gametogenesis
  • Janus kinase
  • Oogenesis
  • Unpaired
  • Unpaired3
  • Wing development

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


Dive into the research topics of 'Pleiotropy of the Drosophila JAK pathway cytokine Unpaired 3 in development and aging'. Together they form a unique fingerprint.

Cite this