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.

中文翻译：

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紧密相关的神经元类型之间的二元命运选择是由Fezf1依赖的有丝分裂后转录开关决定的。

许多神经元类型成对出现，在大多数方面相似，但关键特征不同。在一些称为亚型的视网膜神经元对中，一个成员对亮度的增加做出反应，而另一个对亮度的下降做出响应（ON和OFF响应）。在这里，我们集中于一对这样的星爆无长突细胞（SAC），以探索紧密相关的神经元类型如何多样化。我们发现ON和OFF SAC在它们分离，树突生长和突触形成之前在转录上是不同的。转录阻遏物Fezf1由有丝分裂后的ON SAC选择性表达，并促进ON的命运和基因表达程序，同时抑制OFF的命运和程序。非典型Rho GTPase Rnd3由OFF SAC选择性表达并调节其迁移，但在ON SAC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亚型对多样化的转录程序。