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SMO-M2 mutation does not support cell-autonomous Hedgehog activity in cerebellar granule cell precursors

2019; Nature Portfolio; Volume: 9; Issue: 1 Linguagem: Inglês

10.1038/s41598-019-56057-y

2045-2322

Marialaura Petroni, Maria Sahùn Roncero, Valentina Ramponi, Francesca Fabretti, Vittoria Nicolis di Robilant, Marta Moretti, Vincenzo Alfano, Alessandro Corsi, Simone De Panfilis, Maria Giubettini, Stefano Di Giulio, Carlo Capalbo, Francesca Belardinilli, Anna Coppa, Francesca Sardina, Valeria Colicchia, Flaminia Pedretti, Paola Infante, Beatrice Cardinali, Alessandra Tessitore, Gianluca Canettieri, Enrico De Smaele, Giuseppe Giannini,

Head and Neck Surgical Oncology

Abstract Growth and patterning of the cerebellum is compromised if granule cell precursors do not properly expand and migrate. During embryonic and postnatal cerebellar development, the Hedgehog pathway tightly regulates granule cell progenitors to coordinate appropriate foliation and lobule formation. Indeed, granule cells impairment or defects in the Hedgehog signaling are associated with developmental, neurodegenerative and neoplastic disorders. So far, scant and inefficient cellular models have been available to study granule cell progenitors, in vitro . Here, we validated a new culture method to grow postnatal granule cell progenitors as hedgehog-dependent neurospheres with prolonged self-renewal and ability to differentiate into granule cells, under appropriate conditions. Taking advantage of this cellular model, we provide evidence that Ptch1-KO, but not the SMO-M2 mutation, supports constitutive and cell-autonomous activity of the hedgehog pathway.