RRC ID 28845
Author Sieglitz F, Matzat T, Yuva-Aydemir Y, Neuert H, Altenhein B, Klämbt C.
Title Antagonistic feedback loops involving Rau and Sprouty in the Drosophila eye control neuronal and glial differentiation.
Journal Sci Signal
Abstract During development, differentiation is often initiated by the activation of different receptor tyrosine kinases (RTKs), which results in the tightly regulated activation of cytoplasmic signaling cascades. In the differentiation of neurons and glia in the developing Drosophila eye, we found that the proper intensity of RTK signaling downstream of fibroblast growth factor receptor (FGFR) or epidermal growth factor receptor required two mutually antagonistic feedback loops. We identified a positive feedback loop mediated by the Ras association (RA) domain-containing protein Rau that sustained Ras activity and counteracted the negative feedback loop mediated by Sprouty. Rau has two RA domains that together showed a binding preference for GTP (guanosine 5'-triphosphate)-loaded (active) Ras. Rau homodimerized and was found in large-molecular weight complexes. Deletion of rau in flies decreased the differentiation of retinal wrapping glia and induced a rough eye phenotype, similar to that seen in alterations of Ras signaling. Further, the expression of sprouty was repressed and that of rau was increased by the COUP transcription factor Seven-up in the presence of weak, but not constitutive, activation of FGFR. Together, our findings reveal another regulatory mechanism that controls the intensity of RTK signaling in the developing neural network in the Drosophila eye.
Volume 6(300)
Pages ra96
Published 2013-11-5
DOI 10.1126/scisignal.2004651
PII 6/300/ra96
PMID 24194583
MeSH Animals Blotting, Western COUP Transcription Factors / metabolism Cell Differentiation / physiology* DNA-Binding Proteins / metabolism Drosophila / embryology* Drosophila Proteins / metabolism* Enzyme Activation / physiology Eye / cytology Eye / embryology* Feedback, Physiological / physiology* Gene Expression Regulation / genetics Gene Expression Regulation / physiology Immunohistochemistry In Situ Hybridization Intracellular Signaling Peptides and Proteins / metabolism* Membrane Proteins / metabolism Microscopy, Electron, Transmission Neuroglia / metabolism Protein Binding Protein Structure, Tertiary Receptor Protein-Tyrosine Kinases / metabolism* Receptors, Steroid / metabolism Signal Transduction / physiology*
IF 6.565
Times Cited 10