title: Heterogeneity and Bipotency of Astroglial-Like Cerebellar Progenitors along the Interneuron and Glial Lineages.
abstract: Cerebellar GABAergic interneurons in mouse comprise multiple subsets of morphologically and neurochemically distinct phenotypes located at strategic nodes of cerebellar local circuits. These cells are produced by common progenitors deriving from the ventricular epithelium during embryogenesis and from the prospective white matter (PWM) during postnatal development. However, it is not clear whether these progenitors are also shared by other cerebellar lineages and whether germinative sites different from the PWM originate inhibitory interneurons. Indeed, the postnatal cerebellum hosts another germinal site along the Purkinje cell layer (PCL), in which Bergmann glia are generated up to first the postnatal weeks, which was proposed to be neurogenic. Both PCL and PWM comprise precursors displaying traits of juvenile astroglia and neural stem cell markers. First, we examine the proliferative and fate potential of these niches, showing that different proliferative dynamics regulate progenitor amplification at these sites. In addition, PCL and PWM differ in the generated progeny. GABAergic interneurons are produced exclusively by PWM astroglial-like progenitors, whereas PCL precursors produce only astrocytes. Finally, through in vitro, ex vivo, and in vivo clonal analyses we provide evidence that the postnatal PWM hosts a bipotent progenitor that gives rise to both interneurons and white matter astrocytes.
authors.affiliation: Department of Neuroscience Rita Levi-Montalcini and Neuroscience Institute Cavalieri Ottolenghi, University of Turin, I-10126 Turin, Italy, Neuroscience Institute Cavalieri Ottolenghi, I-10043 Orbassano, Turin, Italy, and.
authors.forename: Elena
authors.identifier: http://orcid.org/0000-0002-3433-1823
authors.initials: E
authors.lastname: Parmigiani
authors.affiliation: Department of Neuroscience Rita Levi-Montalcini and Neuroscience Institute Cavalieri Ottolenghi, University of Turin, I-10126 Turin, Italy, Neuroscience Institute Cavalieri Ottolenghi, I-10043 Orbassano, Turin, Italy, and.
authors.forename: Ketty
authors.initials: K
authors.lastname: Leto
authors.affiliation: Department of Neuroscience Rita Levi-Montalcini and Neuroscience Institute Cavalieri Ottolenghi, University of Turin, I-10126 Turin, Italy, Neuroscience Institute Cavalieri Ottolenghi, I-10043 Orbassano, Turin, Italy, and.
authors.forename: Chiara
authors.initials: C
authors.lastname: Rolando
authors.affiliation: Department of Molecular, Cellular, and Developmental Neurobiology, Cajal Institute, Spanish National Research Council, E-28002 Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Figueres-Oñate
authors.affiliation: Department of Molecular, Cellular, and Developmental Neurobiology, Cajal Institute, Spanish National Research Council, E-28002 Madrid, Spain.
authors.forename: Laura
authors.identifier: http://orcid.org/0000-0002-7154-5687
authors.initials: L
authors.lastname: López-Mascaraque
authors.affiliation: Department of Neuroscience Rita Levi-Montalcini and Neuroscience Institute Cavalieri Ottolenghi, University of Turin, I-10126 Turin, Italy, Neuroscience Institute Cavalieri Ottolenghi, I-10043 Orbassano, Turin, Italy, and annalisa.buffo@unito.it.
authors.forename: Annalisa
authors.identifier: http://orcid.org/0000-0001-7637-0006
authors.initials: A
authors.lastname: Buffo
authors.affiliation: Department of Neuroscience Rita Levi-Montalcini and Neuroscience Institute Cavalieri Ottolenghi, University of Turin, I-10126 Turin, Italy, Neuroscience Institute Cavalieri Ottolenghi, I-10043 Orbassano, Turin, Italy, and.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Rossi
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D018801:CD2 Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D004622:Embryo, Mammalian; D004965:Estrogen Antagonists / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics; D005260:Female; D059330:GABAergic Neurons / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007395:Interneurons / Q000502:physiology*; D008216:Lymphocytic Choriomeningitis / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology; D066127:White Matter / Q000166:cytology / Q000378:metabolism
chemical_list: D000199:Actins; D018801:CD2 Antigens; D004965:Estrogen Antagonists; D027341:Excitatory Amino Acid Transporter 1; C493393:Slc1a3 protein, mouse; D013629:Tamoxifen
keywords: Bergmann glia; cerebellum; mouse brain; multipotent progenitors; neurogenesis; prospective white matter