COUP-TFI controls activity-dependent tyrosine hydroxylase expression in adult dopaminergic olfactory bulb interneurons.
COUP-TFI is an orphan nuclear receptor acting as a strong transcriptional regulator in different aspects of forebrain embryonic development. In this study, we investigated COUP-TFI expression and function in the mouse olfactory bulb (OB), a highly plastic telencephalic region in which continuous integration of newly generated inhibitory interneurons occurs throughout life. OB interneurons belong to different populations that originate from distinct progenitor lineages. Here, we show that COUP-TFI is highly expressed in tyrosine hydroxylase (TH)-positive dopaminergic interneurons in the adult OB glomerular layer (GL). We found that odour deprivation, which is known to downregulate TH expression in the OB, also downregulates COUP-TFI in dopaminergic cells, indicating a possible correlation between TH- and COUP-TFI-activity-dependent action. Moreover, we demonstrate that conditional inactivation of COUP-TFI in the EMX1 lineage results in a significant reduction of both TH and ZIF268 expression in the GL. Finally, lentiviral vector-mediated COUP-TFI deletion in adult-generated interneurons confirmed that COUP-TFI acts cell-autonomously in the control of TH and ZIF268 expression. These data indicate that COUP-TFI regulates TH expression in OB cells through an activity-dependent mechanism involving ZIF268 induction and strongly argue for a maintenance rather than establishment function of COUP-TFI in dopaminergic commitment. Our study reveals a previously unknown role for COUP-TFI in the adult brain as a key regulator in the control of sensory-dependent plasticity in olfactory dopaminergic neurons.
Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123, Torino, Italy.
Serena
S
Bovetti
Sara
S
Bonzano
Donatella
D
Garzotto
Serena Gea
SG
Giannelli
Angelo
A
Iannielli
Maria
M
Armentano
Michèle
M
Studer
Silvia
S
De Marchis
D000818:Animals; D051838:COUP Transcription Factor I / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D007606:Juxtaglomerular Apparatus / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009830:Olfactory Bulb / Q000378:metabolism*; D012683:Sensory Deprivation; D012903:Smell / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*; D000099260:Empty Spiracles Homeobox Proteins
D051838:COUP Transcription Factor I; D051766:Early Growth Response Protein 1; D018398:Homeodomain Proteins; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D000099260:Empty Spiracles Homeobox Proteins; C486109:Egr1 protein, mouse
EMX1 lineage; Juxtaglomerular cells; Mouse; Sensory deprivation; Tyrosine hydroxylase (TH); ZIF268