In order for neural progenitors (NPs) to generate distinct populations of neurons at the right time and place during CNS development, they must switch from undergoing purely proliferative, self-renewing divisions to neurogenic, asymmetric divisions in a tightly regulated manner. In the developing Drosophila optic lobe, neuroepithelial (NE) cells of the outer proliferation center (OPC) are progressively transformed into neurogenic NPs called neuroblasts (NBs) in a medial to lateral proneural wave. The cells undergoing this transition express Lethal of Scute (L'sc), a proneural transcription factor (TF) of the Acheate Scute Complex (AS-C). Here we show that there is also a peak of expression of Asense (Ase), another AS-C TF, in the cells neighboring those with transient L'sc expression. These peak of Ase cells help to identify a new transitional stage as they have lost NE markers and L'sc, they receive a strong Notch signal and barely exhibit NB markers. This expression of Ase is necessary and sufficient to promote the NE to NB transition in a more robust and rapid manner than that of l'sc gain of function or Notch loss of function. Thus, to our knowledge, these data provide the first direct evidence of a proneural role for Ase in CNS neurogenesis. Strikingly, we found that strong Delta-Notch signaling at the lateral border of the NE triggers l'sc expression, which in turn induces ase expression in the adjacent cells through the activation of Delta-Notch signaling. These results reveal two novel non-conventional actions of Notch signaling in driving the expression of proneural factors, in contrast to the repression that Notch signaling exerts on them during classical lateral inhibition. Finally, Suppressor of Hairless (Su(H)), which seems to be upregulated late in the transitioning cells and in NBs, represses l'sc and ase, ensuring their expression is transient. Thus, our data identify a key proneural role of Ase that is integrated with the sequential activities of Delta-Notch signaling, L'sc, and Su(H), driving the progressive transformation of NE cells into NBs.

中文翻译：

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Asense 的一种新颖的原神经功能与 Delta-Notch、L'sc 和 Su(H) 的连续作用相结合，以促进神经上皮向神经母细胞的转变。

为了使神经祖细胞（NP）在中枢神经系统发育过程中在正确的时间和地点产生不同的神经元群体，它们必须以严格调控的方式从纯粹的增殖性、自我更新分裂转变为神经源性、不对称分裂。在发育中的果蝇视叶中，外增殖中心 (OPC) 的神经上皮 (NE) 细胞在内侧至外侧原神经波中逐渐转化为称为神经母细胞 (NB) 的神经源性 NP。经历这种转变的细胞表达 Lethal of Scute (L'sc)，这是 Acheate Scute 复合物 (AS-C) 的原神经转录因子 (TF)。在这里，我们发现，在与短暂表达 L'sc 的细胞相邻的细胞中，另一种 AS-C TF Asense (Ase) 的表达也出现峰值。Ase 细胞的这些峰值有助于识别新的过渡阶段，因为它们失去了 NE 标记和 L'sc，它们接收到强烈的 Notch 信号，几乎没有表现出 NB 标记。Ase 的这种表达对于以比 l'sc 功能获得或 Notch 功能丧失更稳健和更快速的方式促进 NE 到 NB 的转变是必要和充分的。因此，据我们所知，这些数据提供了 Ase 在 CNS 神经发生中的原神经作用的第一个直接证据。引人注目的是，我们发现 NE 侧缘的强 Delta-Notch 信号触发了 l'sc 表达，而 l'sc 表达又通过 Delta-Notch 信号的激活诱导相邻细胞中 ase 的表达。这些结果揭示了Notch信号传导在驱动原神经因子表达方面的两种新颖的非常规作用，这与Notch信号传导在经典侧抑制期间对其施加的抑制形成鲜明对比。最后，无毛抑制因子 (Su(H)) 似乎在过渡细胞和 NB 中上调，抑制 l'sc 和 ase，确保它们的表达是瞬时的。因此，我们的数据确定了 Ase 的关键原神经作用，它与 Delta-Notch 信号传导、L'sc 和 Su(H) 的连续活性相结合，驱动 NE 细胞逐步转化为 NB。