title: Epithelial microRNA-9a regulates dendrite growth through Fmi-Gq signaling in Drosophila sensory neurons.
abstract: microRNA-9 (miR-9) is highly expressed in the nervous system across species and plays essential roles in neurogenesis and axon growth; however, little is known about the mechanisms that link miR-9 with dendrite growth. Using an in vivo model of Drosophila class I dendrite arborization (da) neurons, we show that miR-9a, a Drosophila homolog of mammalian miR-9, downregulates the cadherin protein Flamingo (Fmi) thereby attenuating dendrite development in a non-cell autonomous manner. In miR-9a knockout mutants, the dendrite length of a sensory neuron ddaE was significantly increased. Intriguingly, miR-9a is specifically expressed in epithelial cells but not in neurons, thus the expression of epithelial but not neuronal Fmi is greatly elevated in miR-9a mutants. In contrast, overexpression of Fmi in the neuron resulted in a reduction in dendrite growth, suggesting that neuronal Fmi plays a suppressive role in dendrite growth, and that increased epithelial Fmi might promote dendrite growth by competitively binding to neuronal Fmi. Fmi has been proposed as a G protein-coupled receptor (GPCR), we find that neuronal G protein Gαq (Gq), but not Go, may function downstream of Fmi to negatively regulate dendrite growth. Taken together, our results reveal a novel function of miR-9a in dendrite morphogenesis. Moreover, we suggest that Gq might mediate the intercellular signal of Fmi in neurons to suppress dendrite growth. Our findings provide novel insights into the complex regulatory mechanisms of microRNAs in dendrite development, and further reveal the interplay between the different components of Fmi, functioning in cadherin adhesion and GPCR signalling.
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009024:Morphogenesis; D055495:Neurogenesis / Q000235:genetics; D011984:Sensory Receptor Cells / Q000378:metabolism*
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; C547291:MIRN9 microRNA, Drosophila; D035683:MicroRNAs; C121420:stan protein, Drosophila; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: Flamingo; Gq; dendrite growth; microRNA-9a; non-cell autonomous