The Ecdysone and Notch Pathways Synergistically Regulate Cut at the Dorsal–Ventral Boundary in Drosophila Wing Discs

Abstract

Metazoan development requires coordination of signaling pathways to regulate patterns of gene expression. In Drosophila, the wing imaginal disc provides an excellent model for the study of how signaling pathways interact to regulate pattern formation. The determination of the dorsal/ventral (DV) boundary of the wing disc depends on the Notch pathway, which is activated along the DV boundary and induces the expression of the homeobox transcription factor, Cut. Here, we show that Broad (Br), a zinc-finger transcription factor, is also involved in regulating Cut expression in the DV boundary region. However, Br expression is not regulated by Notch signaling in wing discs, rather, ecdysone signaling is the upstream signal that induces Br for Cut upregulation. Also, we find that the ecdysone-Br cascade upregulates cut-lacZ expression, a reporter containing a 2.7 kb cut enhancer region, implying that ecdysone signaling, similar to Notch, regulates cut at the transcriptional level. Collectively, our findings reveal that the Notch and ecdysone signaling pathways synergistically regulate Cut expression for proper DV boundary formation in the wing disc. Additionally, we show br promotes Delta, a Notch ligand, near the DV boundary to suppress aberrant high Notch activity, indicating further interaction between the two pathways for DV patterning of the wing disc.

Ecdysone signaling induces two phases of cell cycle exit inDrosophilacells

“…6D-E). Loss of Broad also disrupts larval development and wing patterning (Jia et al, 2016), resulting in reduced wing size and altered wing pouch shape. Altogether these data demonstrate that Broad binds stg regulatory regions that drive expression in the wing.…”

Role of co-repressor genomic landscapes in shaping the Notch response

“…These data, along with the strong correlation between SMRTER and Ecdysone Receptor binding, imply that the co-repressors are recruited to the same enhancer via different DNA-binding partners: Hairless via Su(H) and SMRTER via EcR. Crosstalk between Notch and EcR also occurs at the cut enhancer, although this involves Broad rather than EcR [ 51 ] . Thus we conclude that much of the co-localization of SMRTER and Su(H) is likely indicative of genes that are regulated by inputs from the EcR and Notch pathways, although we cannot fully rule out the possibility that SMRTER could act via Su(H) in some circumstances.…”

Developmental regulation of regenerative potential in Drosophila by ecdysone through a bistable loop of ZBTB transcription factors

“…br is activated by ecdysone in wing imaginal discs a few hours after the CW has been reached [25–27]. In wing discs, the Br proteins are required to promote the specification and differentiation of epithelial cells into sensory organ precursors [26]. However, the different roles of the different Br isoforms remain poorly understood.…”