A molecular signaling pathway once thought to maintain cell survival actually helps control epithelial cell shape and organization, US and German researchers show in two fruit fly studies published by
"In nature, different organisms sculpt epithelial sheets into a bewildering array of forms, but relatively little is known about the mechanisms involved," coauthor Matthew Gibson of Harvard University told
Gibson and senior coauthor Norbert Perrimon screened for genetic factors that control epithelial cell shape during
One experimental line developed defects in establishing or maintaining pseudostratified columnar shape in medial regions of the wing imaginal disc, resulting in cystlike epithelial extrusions. Recombination mapping against a set of P-element insertions pinpointed the mutation to cytological interval 25D-25F, which bears the decapentaplegic (DPP) receptor
Independently, Jie Shen and Christian Dahmann at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, investigated what role DPP plays in wing epithelial cells. Prior experiments suggested DPP's role was to control cell survival, since reduced DPP signaling activated the JNK stress signaling pathway and apoptosis. Shen and Dahmann analyzed
"It is surprising to see that mutant cells extruded from the epithelial sheet can survive and even differentiate," Dahmann said. Both research teams found mutant
The US team found that prior studies often triggered recombination with heat shock instead of a tissue-specific driver, suggesting that either heat shock enhanced
"The Gibson and Perrimon paper shed light on why DPP's function was obscured before in a well-trodden path of experiments by this heat shock protocol that puts cells in a stressful condition when they were sensitive," said Alfonso Martinez-Arias at the University of Cambridge, who did not participate in these experiments.
Both research teams found that in stained micrographs,
Future research will involve further genetic screens and transcriptional profiling experiments designed to connect the DPP pathway with morphogenesis effectors, particularly molecules that could influence the integrity of the apical microtubule cytoskeleton and F-actin meshwork.
"This work is screaming for someone to look for any GTPases regulated by DPP," since GTPases regulate the cytoskeleton, said Valerie Weaver of the University of Pennsylvania, who did not participate in these experiments.
While extrusion could result from cytoskeletal effects, "it is just as likely that extrusion is due to an underlying defect in cell adhesion and the cytoskeletal effects are secondary," Gibson added. "We're interested in possible roles for cell-matrix interactions."