Polycomb Ezh2 controls the fate of GABAergic neurons in the embryonic cerebellum
Polycomb Ezh2 controls the fate of GABAergic neurons in the embryonic cerebellum
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DOI：
10.1242/dev.132902
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发表时间：
2016-06-01
期刊：
影响因子：
4.6
通讯作者：
Sartorelli, Vittorio
中科院分区：
文献类型：
--
作者：
Feng, Xuesong;Juan, Aster H.;Sartorelli, Vittorio
虽然信号通路和转录因子之间的遗传相互作用已经在很大程度上被解码，但关于小脑发育的表观遗传调控仍有很多东西有待了解。在这里，我们报告说，小脑删除Ezh 2，PRC 2复合物的甲基转移酶亚基，导致减少H3 K27 me 3和深刻的转录失调，包括一组直接参与小脑神经元细胞类型的规范和分化的转录因子。这种转录变化导致GABA能中间神经元增加和浦肯野细胞减少。转录的变化也抑制了菱形唇来源的颗粒前体细胞的增殖。这两种细胞类型的丧失最终导致小脑发育不全。这些发现表明Ezh 2/PRC 2在调节小脑生发区的神经发生中起着至关重要的作用。
Although the genetic interactions between signaling pathways and transcription factors have been largely decoded, much remains to be learned about the epigenetic regulation of cerebellar development. Here, we report that cerebellar deletion of Ezh2, the methyltransferase subunit of the PRC2 complex, results in reduced H3K27me3 and profound transcriptional dysregulation, including that of a set of transcription factors directly involved in cerebellar neuronal cell-type specification and differentiation. Such transcriptional changes lead to increased GABAergic interneurons and decreased Purkinje cells. Transcriptional changes also inhibit the proliferation of granule precursor cells derived from the rhombic lip. The loss of both cell types ultimately results in cerebellar hypoplasia. These findings indicate Ezh2/PRC2 plays crucial roles in regulating neurogenesis from both cerebellar germinal zones.