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Publication : Mature Purkinje cells require the retinoic acid-related orphan receptor-α (RORα) to maintain climbing fiber mono-innervation and other adult characteristics.

First Author  Chen XR Year  2013
Journal  J Neurosci Volume  33
Issue  22 Pages  9546-62
PubMed ID  23719821 Mgi Jnum  J:198656
Mgi Id  MGI:5498608 Doi  10.1523/JNEUROSCI.2977-12.2013
Citation  Chen XR, et al. (2013) Mature Purkinje cells require the retinoic acid-related orphan receptor-alpha (RORalpha) to maintain climbing fiber mono-innervation and other adult characteristics. J Neurosci 33(22):9546-62
abstractText  Neuronal maturation during development is a multistep process regulated by transcription factors. The transcription factor RORalpha (retinoic acid-related orphan receptor alpha) is necessary for early Purkinje cell (PC) maturation but is also expressed throughout adulthood. To identify the role of RORalpha 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 RORalpha-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 RORalpha 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.
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