Journal of Neuroscience, E. Parmigiani

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Journal of Neuroscience, E. Parmigiani

Journal of Neuroscience, May 2015

Heterogeneity and Bipotency of Astroglial-Like Cerebellar Progenitors along the Interneuron and Glial Lineages

Elena Parmigiani 1,2 , Ketty Leto 1,2 , Chiara Rolando 1,2 , María Figueres-Oñate 3 , Laura López-Mascaraque 3 , Annalisa Buffo 1,2 , and Ferdinando Rossi 1,2,†

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. 
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Progenitors in the Purkinje cell layer (figure on the top) and in the prospective white matter (bottom of the figure) display distinct fate potential. Namely, no parvalbumin+ interneurons, but only GFAP+astrocytes derive from selectively labelled radial progenitors in the PCL. On the contrary,  progenitors exclusively in the PWM are able to generate both astrocytes and interneurons, as demonstrated by in vivo clonal analysis.
1 Department of Neuroscience Rita Levi-Montalcini and Neuroscience Institute Cavalieri Ottolenghi, University of Turin, I-10126 Turin, Italy,
2 Neuroscience Institute Cavalieri Ottolenghi, I-10043 Orbassano, Turin, Italy, and 3Department of Molecular, Cellular
3 Developmental Neurobiology, Cajal Institute, Spanish National Research Council, E-28002 Madrid, Spain