title: Mature Purkinje cells require the retinoic acid-related orphan receptor-α (RORα) to maintain climbing fiber mono-innervation and other adult characteristics.
abstract: Neuronal maturation during development is a multistep process regulated by transcription factors. The transcription factor RORα (retinoic acid-related orphan receptor α) is necessary for early Purkinje cell (PC) maturation but is also expressed throughout adulthood. To identify the role of RORα in mature PCs, we used Cre-lox mouse genetic tools in vivo that delete it specifically from PCs between postnatal days 10-21. Up to 14 d of age, differences between mutant and control PCs were not detectable: both were mono-innervated by climbing fibers (CFs) extending along their well-developed dendrites with spiny branchlets. By week 4, mutant mice were ataxic, some PCs had died, and remaining PC soma and dendrites were atrophic, with almost complete disappearance of spiny branchlets. The innervation pattern of surviving RORα-deleted PCs was abnormal with several immature characteristics. Notably, multiple functional CF innervation was reestablished on these mature PCs, simultaneously with the relocation of CF contacts to the PC soma and their stem dendrite. This morphological modification of CF contacts could be induced even later, using lentivirus-mediated depletion of rora from adult PCs. These data show that the late postnatal expression of RORα cell-autonomously regulates the maintenance of PC dendritic complexity, and the CF innervation status of the PC (dendritic vs somatic contacts, and mono-innervation vs multi-innervation). Thus, the differentiation state of adult neurons is under the control of transcription factors; and in their absence, adult neurons lose their mature characteristics and acquire some characteristics of an earlier developmental stage.
authors.affiliation: UPMC Université Paris 06, UMR 7102, 75005 Paris, France.
authors.forename: Xiao Ru
authors.initials: XR
authors.lastname: Chen
authors.forename: Nicolas
authors.initials: N
authors.lastname: Heck
authors.forename: Ann M
authors.initials: AM
authors.lastname: Lohof
authors.forename: Christelle
authors.initials: C
authors.lastname: Rochefort
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Morel
authors.forename: Rosine
authors.initials: R
authors.lastname: Wehrlé
authors.forename: Mohamed
authors.initials: M
authors.lastname: Doulazmi
authors.forename: Serge
authors.initials: S
authors.lastname: Marty
authors.forename: Vidjeacoumary
authors.initials: V
authors.lastname: Cannaya
authors.forename: Hasan X
authors.initials: HX
authors.lastname: Avci
authors.forename: Jean
authors.initials: J
authors.lastname: Mariani
authors.forename: Laure
authors.initials: L
authors.lastname: Rondi-Reig
authors.forename: Guilan
authors.initials: G
authors.lastname: Vodjdani
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Sherrard
authors.forename: Constantino
authors.initials: C
authors.lastname: Sotelo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dusart
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D001522:Behavior, Animal / Q000502:physiology; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D007398:Interpersonal Relations; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D053580:Muscle Strength / Q000235:genetics / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009412:Nerve Fibers / Q000502:physiology*; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D004856:Postural Balance / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics
chemical_list: D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D012097:Repressor Proteins; C539739:Rora protein, mouse; C493477:Slc17a6 protein, mouse; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D004247:DNA