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Ontogenesis of glial diversity in the cerebellum as revealed through quantitative in vivo clonal analyses

AuthorsCerrato,V.; Parmigiani, E.; Figueres-Oñate, Maria; Betizeau, M.; Ossola, C.; Luzzati, F.; López-Mascaraque, Laura; Buffo, A.
Cell proliferation and lineage
Issue Date10-Jul-2019
CitationGLIA 2O19: IXIV European Meeting on Glial Cells in Health and disease in Porto, Portugal, 10-13 July, 2019
AbstractIn the cerebellum, astrocytes (AS) and oligodendrocytes (OLs) are characterized by a peculiar phenotypic heterogeneity, closely related to specific functional features. Nevertheless, the ontogenesis of this glial diversity remains poorly understood. By combining in vivo clonal analyses employing StarTrack plasmids and Confetti mice withproliferation studies, we have recently demonstrated that the major cerebellar AS types derive from embryonic and postnatal progenitors with diverse lineage potentials. Moreover, AS heterogeneity appeared to emerge according to an unprecedented and remarkably orderly developmental program, likely driven by deterministic components as suggested by in silico simulations. Similar StarTrack clonal analyses are now being applied to elucidate the origins, clonal relationships, and spatial distribution of cerebellar OLs born at distinct developmental stages. While AS clones showed a time-dependent allocation first to the hemispheres and then to the vermis, preliminary data indicate that OL clones are not medio-laterally compartmentalised, being capable of populating either of the two regions independently from their developmental origin. This suggests that the two progenitor pools, originally spatially segregated, also follow distinct guidance mechanisms to populate different cerebellar territories within the same developmental time window. On the other side, both AS and OLs displayed a similar behaviour along the antero-posterior axis: cells belonging to distinct clones rarely intermingled and, rather, clustered to populate discrete cerebellar lobules, thereby suggesting that each AS or OL clone is involved in the functional maturation and/or maintenance of specific neural circuit compartments, with poor contributions from others. Last, similarly to AS clones characterized by stereotyped architectures and recurrent modularities, immunohistochemical and morphological analyses of the cells strikingly highlighted that OL clones have a constant relative contribution of immature and mature cells, in favour of the mature part. While the modularity in AS clones was demonstrated to reflect layer-specific dynamics of postnatal proliferation/differentiation, what determines the equilibrium between immature and post-mitotic cells in OL clones is unknown. It will be interesting to investigate whether it reflects intrinsic properties of the progenitors themselves or it depends upon extrinsic cues, such as the surrounding axonal availability.
DescriptionTrabajo presentado en GLIA 2019: XIV European Meeting on Glial Cells in Health and disease en Oporto el 10 de Julio de 2019.
Appears in Collections:(IC) Comunicaciones congresos
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