期刊
DEVELOPMENT
卷 149, 期 6, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.200159
关键词
Hedgehog; Signal transduction; Pathway modulation; Drosophila
资金
- Northwestern University
- Centre national de la recherche scientifique
- Universite de Paris
- Fondation ARC pour la Recherche sur le Cancer [1112]
Morphogen gradients require robustness and can be tailored for specific tissues through negative regulators and feedback loops. In the Drosophila wing imaginal disc, genes like Engrailed and Roadkill modulate Hh signaling and affect the formation of the Hh gradient.
Morphogen gradients need to be robust, but may also need to be tailored for specific tissues. Often this type of regulation is carried out by negative regulators and negative feedback loops. In the Hedgehog (Hh) pathway, activation of patched (ptc) in response to Hh is part of a negative feedback loop limiting the range of the Hh morphogen. Here, we show that in the Drosophila wing imaginal disc two other known Hh targets genes feed back to modulate Hh signaling. First, anterior expression of the transcriptional repressor Engrailed modifies the Hh gradient by attenuating the expression of the Hh pathway transcription factor cubitus interruptus (ci), leading to lower levels of ptc expression. Second, the E-3 ligase Roadkill shifts the competition between the full-length activator and truncated repressor forms of Ci by preferentially targeting full-length Ci for degradation. Finally, we provide evidence that Suppressor of fused, a negative regulator of Hh signaling, has an unexpected positive role, specifically protecting full-length Ci but not the Ci repressor from Roadkill.
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