Postmitotic Hoxa5 Expression Specifies Pontine Neuron Positional Identity and Input Connectivity of Cortical Afferent Subsets
Postmitotic Hoxa5 Expression Specifies Pontine Neuron Positional Identity and Input Connectivity of Cortical Afferent Subsets
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DOI：
10.1016/j.celrep.2020.107767
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发表时间：
2020-06-16
期刊：
影响因子：
8.8
通讯作者：
Rijli, Filippo M.
中科院分区：
文献类型：
--
作者：
Maheshwari, Upasana;Kraus, Dominik;Rijli, Filippo M.
哺乳动物小脑前脑桥核(PN)在向小脑传递皮质信息方面起主要作用。在皮质传入和小脑前神经元之间建立有序连接模式的分子决定因素在很大程度上是未知的。我们发现，Hox5转录因子的表达是在迁移开始时在有丝分裂后PN神经元的特定亚群中诱导的。Hox5的诱导是通过对维甲酸信号的响应实现的，导致Jmjd3依赖的多梳染色质的去抑制和3D构象变化。Hoxa5驱动神经元在PN中的后部定居，在那里它们是主要携带肢体躯体感觉的皮质神经元亚群的单通道靶点。此外，Hoxa5在PN神经元迁移后的异位表达足以吸引不同位置的皮质体感输入，并避免视觉传入。转录组分析进一步表明，Hoxa5参与了电路的形成。因此，Hoxa5协调皮质-小脑通路中PN神经元亚群的有丝分裂后指定、迁移、定居位置和亚路组装。
The mammalian precerebellar pontine nucleus (PN) has a main role in relaying cortical information to the cerebellum. The molecular determinants establishing ordered connectivity patterns between cortical afferents and precerebellar neurons are largely unknown. We show that expression of Hox5 transcription factors is induced in specific subsets of postmitotic PN neurons at migration onset. Hox5 induction is achieved by response to retinoic acid signaling, resulting in Jmjd3-dependent derepression of Polycomb chromatin and 3D conformational changes. Hoxa5 drives neurons to settle posteriorly in the PN, where they are monosynaptically targeted by cortical neuron subsets mainly carrying limb somatosensation. Furthermore, Hoxa5 postmigratory ectopic expression in PN neurons is sufficient to attract cortical somatosensory inputs regardless of position and avoid visual afferents. Transcriptome analysis further suggests that Hoxa5 is involved in circuit formation. Thus, Hoxa5 coordinates postmitotic specification, migration, settling position, and subcircuit assembly of PN neuron subsets in the cortico-cerebellar pathway.