Shade enhancers, a class of redundant enhancers uncovered by functional JAK-STAT pathway dissection

Authors

Sanchez-Higueras, C., Terron-Gonzalez, L., Barcenilla-Merino, D., Garcia-Ferres, M. S., Marrufo-Mena, A., Sotillos, S., C-G Hombria, J.

Abstract

JAK-STAT signalling pathway activation relies mostly on the transcriptional regulation of its ligands. The pathway, conserved in vertebrates and invertebrates, is required for the development and homeostasis of various organs. In contrast to the complexity of the vertebrate pathway, with a multiplicity of ligands, receptors, kinases and transcription factors, the simplicity of the Drosophila pathway with only three ligands (Upd1, Upd2 and Upd3), a single receptor (Dome), a JAK kinase (Hop) and a STAT transcription factor (STAT92E) facilitates the genetic study of its multiple functions. To discover how, when and where the Upd1 ligand performs each organogenetic function, we have searched for the different enhancers controlling its dynamic spatio-temporal regulation and used them to generate minigenes replicating specific stages of Upd1 expression. The combination of these minigenes with mutations deleting all three Upd ligands, allowed us to identify the timing when the various embryonic functions are mediated, including head involution, tracheae, corpora allata and prothoracic gland specification, posterior spiracle formation and hindgut elongation. We uncover most of the enhancers controlling STAT activation during embryonic organogenesis and those driving activation in the adult testis and the ovary. As expected, we identified redundant shadow enhancers but, interestingly, we found a different type of redundant enhancers that mediate identical developmental functions although driving completely different expression patterns. We name this new class of functionally redundant enhancers driving different expression as shade enhancers. We propose shade enhancers provide evolutionary plasticity as they could allow the pattern of gene expression to diversify without altering the underlying body plan.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 03 Oct 2026.

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