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

Sci Rep 2019 12 23;9(1):19623. Epub 2019 Dec 23.

Department of Molecular Medicine, University La Sapienza, 00161, Rome, Italy.

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.

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http://dx.doi.org/10.1038/s41598-019-56057-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928071PMC
December 2019
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