The histone H3 lysine 27 (H3K27) demethylase Kdm6b (Jmjd3) can promote cellular differentiation, however its physiological functions in neurons remain to be fully determined. We studied the expression and function of Kdm6b in differentiating granule neurons of the developing postnatal mouse cerebellum. At postnatal day 7, Kdm6b is expressed throughout the layers of the developing cerebellar cortex, but its expression is upregulated in newborn cerebellar granule neurons (CGNs). Atoh1-Cre mediated conditional knockout of Kdm6b in CGN precursors either alone or in combination with Kdm6a did not disturb the gross morphological development of the cerebellum. Furthermore, RNAi-mediated knockdown of Kdm6b in cultured CGN precursors did not alter the induced expression of early neuronal marker genes upon cell cycle exit. By contrast, knockdown of Kdm6b significantly impaired the induction of a mature neuronal gene expression program, which includes gene products required for functional synapse maturation. Loss of Kdm6b also impaired the ability of Brain-Derived Neurotrophic Factor (BDNF) to induce expression of Grin2c and Tiam1 in maturing CGNs. Taken together, these data reveal a previously unknown role for Kdm6b in the postmitotic stages of CGN maturation and suggest that Kdm6b may work, at least in part, by a transcriptional mechanism that promotes gene sensitivity to regulation by BDNF.

组蛋白H3赖氨酸27（H3K27）脱甲基酶Kdm6b（Jmjd3）可以促进细胞分化，但是其在神经元中的生理功能仍有待完全确定。我们研究了Kdm6b在发育中的出生后小鼠小脑的颗粒神经元分化中的表达和功能。出生后第7天，Kdm6b在整个发育中的小脑皮层中表达，但其表达在新生小脑颗粒神经元（CGNs）中上调。单独或与Kdm6a组合的CGN前体中Atoh1- Cre介导的Kdm6b的条件性敲除不会干扰小脑的总体形态发育。此外，RNAi介导的Kdm6b的敲低在培养的CGN前体中，细胞周期出口退出时，其未改变早期神经元标记基因的诱导表达。相比之下，Kdm6b的敲低大大损害了成熟神经元基因表达程序的诱导，该程序包括功能性突触成熟所需的基因产物。Kdm6b的丢失也损害了脑源性神经营养因子（BDNF）诱导成熟CGNs中Grin2c和Tiam1表达的能力。综上所述，这些数据揭示了Kdm6b在CGN成熟的有丝分裂后阶段中以前未知的作用，并暗示Kdm6b可能至少部分地通过促进基因对BDNF调控的基因敏感性的转录机制起作用。