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Abstract：
Notch signaling is an evolutionarily conserved pathway for specifying binary neuronal fates, yet how it specifies different fates in different contexts remains elusive. In our accompanying paper, using the Drosophila lamina neuron types (L1-L5) as a model, we show that the primary homeodomain transcription factor (HDTF) Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates. Here we test the hypothesis that Notch signaling enables Bsh to differentially specify L4 and L5 fates. We show asymmetric Notch signaling between newborn L4 and L5 neurons, but they are not siblings; rather, Notch signaling in L4 is due to Delta expression in adjacent L1 neurons. While Notch signaling and Bsh expression are mutually independent, Notch is necessary and sufficient for Bsh to specify L4 fate over L5. The NotchON L4, compared to NotchOFF L5, has a distinct open chromatin landscape which allows Bsh to bind distinct genomic loci, leading to L4-specific identity gene transcription. We propose a novel model in which Notch signaling is integrated with the primary HDTF activity to diversify neuron types by directly or indirectly generating a distinct open chromatin landscape that constrains the pool of genes that a primary HDTF can activate.
摘要：
Notch信号是一种进化上保守的途径，用于指定二元神经元的命运，然而，它如何在不同的背景下指定不同的命运仍然难以捉摸。在我们的论文中，使用果蝇层神经元类型（L1-L5）作为模型，我们显示初级同源域转录因子（HDTF）Bsh激活次级HDTFsAp（L4）和Pdm3（L5），并指定L4/L5神经元命运。在这里，我们测试了Notch信号使Bsh能够区分指定L4和L5命运的假设。我们显示了新生L4和L5神经元之间的不对称Notch信号，但他们不是兄弟姐妹，L4中的Notch信号传导是由于相邻L1神经元中的Delta表达。虽然Notch信号和Bsh表达是相互独立的，陷波对于Bsh指定L5上的L4命运是必要且足够的。与NotchOFFL5相比，NotchONL4具有独特的开放染色质景观，允许Bsh结合不同的基因组基因座，导致L4特异性身份基因转录。我们提出了一种新的模型，其中Notch信号与初级HDTF活性整合，通过直接或间接产生独特的开放染色质景观来使神经元类型多样化，从而限制初级HDTF可以激活的基因库。
