GSE111872
The Transcriptional Regulator SnoN Promotes the Proliferation of Granule Neuron Precursors in the Brain in a Temporally Specific Manner
Control of neuronal precursor cell proliferation is essential for normal brain development, and deregulation of this fundamental developmental event contributes to brain diseases. Typically, neuronal precursor cell proliferation extends over long periods of time during brain development. However, how neuronal precursor proliferation is regulated in a temporally specific manner remains to be elucidated. Here, we report that conditional knockout of the transcriptional regulator SnoN in granule neuron precursors in the mouse cerebellum robustly inhibits the proliferation of these cells and promotes their cell cycle exit specifically at later stages of cerebellar development in the postnatal brain. In gene profiling studies, SnoN promotes the expression of a program of cell proliferation genes in granule neuron precursors, whose pattern of expression and gene promoter-associated histone marks temporally correlates with SnoN-regulation of granule precursor cell proliferation. In behavior analyses, conditional knockout of SnoN impairs cerebellar-dependent learning in a delayed eye-blink conditioning paradigm, suggesting that SnoN-regulation of granule neuron precursor proliferation bears functional consequences at the organismal level. Our findings define a novel function for the major transcriptional regulator SnoN in the temporal control of granule precursor cell proliferation in the mammalian brain. Overall design: Total RNA-seq from the cerebellum of SnoN conditional knockout and wildtype mice