The Drosophila JAK-STAT pathway

Abstract

The conservation of signaling cascades between humans and Drosophila, over more than 500 million years of evolutionary time, means that the genetic tractability of the fly can be used to its full advantage to understand the functional requirements for JAK-STAT pathway signaling across species. Here we review the background to how the pathway was first identified and the first characterization of JAK-STAT pathway phenotypes in the Drosophila system, highlighting the molecular, functional, and disease-related conservation of the pathway.

Figure 1. The embryonic cuticle phenotype associated with wild-type (A) and loss of JAK-STAT pathway activity (B)—in this case involving the removal of maternally contributed STAT92E. Head skeleton (HS) and posterior spiracles (PS) are both disrupted in pathway mutants. In addition, of the abdominal segments 1 to 8 (a1 to a8) a4 and a5 are missing and a8 reduced in the stat92E mutant. Figure reproduced with permission from reference .

Figure 2. Third instar larvae either wild-type for the Hop locus (A) or carrying one copy of the gain-of-function Hop^T42 allele (B). Larvae with activated Hop alleles have increased numbers of circulating hemocytes which inappropriately differentiate into lamellocytes which then frequently form black melanized tumors (visible in [B]). See text for details.

About Dr Martin Zeidler. Dr Zeidler received a BSc from the University of Sussex and undertook his PhD research at the European Molecular Biology Laboratory (EMBL) in Heidelberg Germany. Working on the developmental genetics of Drosophila, he then moved to the laboratory of Prof Norbert Perrimon at Harvard Medical School where he first started studying the roles of JAK-STAT pathway signaling in the fruit fly. Founding his own lab at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, he was involved in genetic and genome-scale RNAi screens for regulators of JAK-STAT pathway activity. Moving to the University of Sheffield in 2006, he holds a Cancer Research UK Senior Cancer Research Fellowship and works within the MRC Centre for Developmental and Biomedical Genetics trying to work out what all the JAK-STAT regulatory genes actually do.

About Dr Nina Bausek. Dr Nina Bausek received an MSc from the University of Vienna, Austria. She was selected for the joint PhD program of the Institute of Molecular Pathology (IMP) and University of Vienna, Austria, studying the avian zona pellucida. Changing countries and model organism, she joined the lab of Dr Helen White-Cooper at the Department of Zoology, Oxford University to work on spermatogenesis-specific genes in Drosophila. Appreciating the scientific advantages of the fruit fly, she moved to the lab of Dr Martin Zeidler at the University of Sheffield, where she is funded by Cancer Research UK to specifically work on JAK-STAT downstream targets.