Cerebellar granule neuron progenitors are the source of Hk2 in the postnatal cerebellum
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KeywordsMedulloblastoma Granule Cell Layer Aerobic Glycolysis Cerebellar Granule Neuron Cerebellar Development
A response to Leprince: The role of Bergmann glial cells in cerebellar development. Cancer & Metabolism 2013, 1:14
We recently demonstrated that developmentally regulated aerobic glycolysis is integral to the normal process of postnatal neurogenesis and becomes co-opted in medulloblastoma. In our work, we concluded that Hexokinase 2 (Hk2), which we found to be required for Shh-induced aerobic glycolysis, was expressed specifically by cerebellar granule neuron progenitors (CGNPs). We observed altered migration of CGNPs in hGFAP-cre;Hk2f/f mice and attributed this aspect of the phenotype to premature differentiation of CGNPs caused by loss of aerobic glycolysis. In response to our work, LePrince draws attention to the role of Bergmann glia in cerebellar development.
LePrince raises the important point that cerebellar granule neurons (CGNPs) do not develop in isolation but rather interact critically with the Bergmann glia. The Bergmann glia establish a radial scaffold on which the CGNPs migrate from the external to the internal granule cell layer [1, 2]. Our data are consistent with the possibility that conditional deletion of Hk2 disrupts the interaction through which CGNPs are guided in their migration by the processes of the Bergmann glia. The idea that cellular metabolic patterns may modulate developmental signaling between CGNPs and glia fits well with our finding that developmental signaling between Purkinje cells and CGNPs, mediated by Shh, regulates CGNP metabolism.
We appreciate the emphasis that LePrince places on the role of Bergmann glia in directing CGNP migration. Our data identify the CGNPs as the principal cells actuating Hk2-mediated aerobic glycolysis. The possibility that loss of aerobic glycolysis disrupts the interaction of CGNPs with the Bergmann glia deserves further investigation.
Mice were handled Mice were handled in compliance with the guidelines of the University of North Carolina Animal Care and Use Committee (IACUC#10-126). Brains from P9 wild type BL6 pups were fixed in 4% formaldehyde, embedded in paraffin and 5 mm sagittal sections were cut and placed on glass slides. Slides were processed and stained using the RNAscope 2.0 kit (cat#310095, Advanced Cell Diagnostics, Hayward, CA) according to manufacturer instructions, with the insertion of a 10 minute DNAse treatment step at 40°C before hybridization, using RNAse-free DNAse 1u/μl in 1xDNAse buffer (Cat# M6101, Promega, Madison, WI).
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