关键词: Fezf1 ON-OFF Rnd3 amacrine cell fate migration polarization retina starburst transcription factor

Mesh : Amacrine Cells / chemistry metabolism Animals Animals, Newborn Female HEK293 Cells Humans Interneurons / chemistry metabolism Mice Mice, 129 Strain Mice, Transgenic Mitosis / physiology Pregnancy Repressor Proteins / analysis biosynthesis genetics Transcription, Genetic / physiology

来  源:   DOI:10.1016/j.neuron.2019.11.002   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Many neuronal types occur as pairs that are similar in most respects but differ in a key feature. In some pairs of retinal neurons, called paramorphic, one member responds to increases and the other to decreases in luminance (ON and OFF responses). Here, we focused on one such pair, starburst amacrine cells (SACs), to explore how closely related neuronal types diversify. We find that ON and OFF SACs are transcriptionally distinct prior to their segregation, dendritic outgrowth, and synapse formation. The transcriptional repressor Fezf1 is selectively expressed by postmitotic ON SACs and promotes the ON fate and gene expression program while repressing the OFF fate and program. The atypical Rho GTPase Rnd3 is selectively expressed by OFF SACs and regulates their migration but is repressed by Fezf1 in ON SACs, enabling differential positioning of the two types. These results define a transcriptional program that controls diversification of a paramorphic pair.
摘要:
许多神经元类型成对出现,在大多数方面相似,但在关键特征上有所不同。在一些视网膜神经元中,叫做异形,一个成员对亮度的增加做出响应,另一个成员对亮度的降低做出响应(ON和OFF响应)。这里,我们专注于这样的一对,星爆无长突细胞(SAC),探索密切相关的神经元类型如何多样化。我们发现ON和OFFSAC在分离之前在转录上是不同的,树突状生长,和突触形成。转录阻遏物Fezf1通过有丝分裂后的ONSAC选择性表达,并促进ON命运和基因表达程序,同时抑制OFF命运和程序。非典型RhoGTPaseRnd3由OFFSACs选择性表达并调节其迁移,但在ONSACs中被Fezf1抑制,实现两种类型的差分定位。这些结果定义了控制异形对的多样化的转录程序。
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