Abstract:
Proper formation of the hippocampus is crucial for the brain to execute memory and learning functions. However, many questions remain regarding how pyramidal neurons (PNs) of the hippocampus mature and precisely position. Here we revealed that Setd2, the methyltransferase for histone 3 lysine 36 trimethylation (H3K36me3), is essential for the precise localization and maturation of PNs in the hippocampal CA1. The ablation of Setd2 in neural progenitors leads to irregular lamination of the CA1 and increased numbers of PNs in the stratum oriens. Setd2 deletion in postmitotic neurons causes mislocalization and immaturity of CA1 PNs. Transcriptome analyses revealed that SETD2 maintains the expressions of clustered protocadherin (cPcdh) genes. Together, Setd2 is required for proper hippocampal lamination and maturation of CA1 PNs.
摘要:
海马体的适当形成对于大脑执行记忆和学习功能至关重要。然而,关于海马的锥体神经元(PNs)如何成熟和精确位置,仍然存在许多问题。在这里,我们揭示了Sett2,组蛋白3赖氨酸36三甲基化(H3K36me3)的甲基转移酶,对于海马CA1中PNs的精确定位和成熟至关重要。Sett2在神经祖细胞中的消融导致CA1的不规则分层和地层中PN的数量增加。有丝分裂后神经元中的Sett2缺失会导致CA1PN的定位错误和不成熟。转录组分析显示,SETD2维持了成簇的原钙粘蛋白(cPcdh)基因的表达。一起,Sett2是适当的海马分层和CA1PN成熟所必需的。