RRC ID 53818
Author Eusebio N, Tavares L, Pereira PS.
Title CtBP represses Dpp-dependent Mad activation during Drosophila eye development.
Journal Dev Biol
Abstract Complex networks of signaling pathways maintain the correct balance between positive and negative growth signals, ensuring that tissues achieve proper sizes and differentiation pattern during development. In Drosophila, Dpp, a member of the TGFβ family, plays two main roles during larval eye development. In the early eye primordium, Dpp promotes growth and cell survival, but later on, it switches its function to induce a developmentally-regulated cell cycle arrest in the G1 phase and neuronal photoreceptor differentiation. To advance in the identification and characterization of regulators and targets of Dpp signaling required for retinal development, we carried out an in vivo eye-targeted double-RNAi screen to identify punt (Type II TGFβ receptor) interactors. Using a set of 251 genes associated with eye development, we identified CtBP, Dad, Ago and Brk as punt genetic interactors. Here, we show that downregulation of Ago, or conditions causing increased tissue growth including overexpression of Myc or CyclinD-Cdk4 are sufficient to partially rescue punt-dependent growth and photoreceptor differentiation. Interestingly, we show a novel role for the transcriptional co-repressor CtBP in inhibiting Dpp-dependent Mad activation by phosphorylation, downstream or in parallel to Dad, the inhibitory Smad. Furthermore, CtBP downregulation activates JNK signaling pathway, implying a complex regulation of signaling pathways by CtBP during eye development.
Volume 442(1)
Pages 188-198
Published 2018-10-1
DOI 10.1016/j.ydbio.2018.07.018
PII S0012-1606(17)30872-2
PMID 30031756
MeSH Activin Receptors, Type II / genetics Activin Receptors, Type II / metabolism Activin Receptors, Type II / physiology* Alcohol Oxidoreductases / metabolism Alcohol Oxidoreductases / physiology* Animals Cell Differentiation / genetics Cyclin-Dependent Kinase 4 DNA-Binding Proteins / metabolism* DNA-Binding Proteins / physiology* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila Proteins / physiology* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Eye / embryology Eye / metabolism Gene Expression Regulation, Developmental / genetics Morphogenesis Organogenesis Repressor Proteins / metabolism Signal Transduction / genetics Transcription Factors / metabolism* Transcription Factors / physiology Transforming Growth Factor beta / metabolism
IF 2.896
Times Cited 1
Drosophila 15010R-2 8224R-3 16987R-2 12399R-1 1560R-2 2262R-2 2262R-1 7233R-4 7233R-1 7904R-3 11062R-1