Notch resolves mixed neural identities in the zebrafish epiphysis
Notch resolves mixed neural identities in the zebrafish epiphysis
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DOI：
10.1242/dev.013482
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发表时间：
2008-07-15
期刊：
影响因子：
4.6
通讯作者：
Blader, Patrick
中科院分区：
文献类型：
--
作者：
Cau, Elise;Quillien, Aurelie;Blader, Patrick
Notch 活性的操纵改变了脊椎动物神经元谱系中的神经元亚型身份。尽管如此，Notch 活性是通过调节神经发生的时间来使细胞命运多样化，还是直接作用于神经元亚型规范，仍然存在争议。在这里，我们讨论了 Notch 在斑马鱼骨骺中的作用，斑马鱼骨骺是一种仅包含两种神经亚型的简单结构：投射神经元和光感受器。减少Notch通路的活性会导致投射神经元过多，而牺牲光感受器，并且保留混合身份的细胞也会增加。然而，尽管强制激活该通路会抑制投射神经元的命运，但它不会促进光感受器的身份。正如生日实验表明，投射神经元和光感受器是同时诞生的，Notch 在神经元规范过程中直接起作用，而不是通过控制神经发生的时间。最后，我们的数据表明，光感受器命运规范需要两种不同的信号：一种用于诱导光感受器命运，另一种涉及Notch，用于抑制投射神经元特征。我们提出了一种新颖的模型，其中 Notch 通过抑制不需要的遗传程序来解决混合神经身份问题。
Manipulation of Notch activity alters neuronal subtype identity in vertebrate neuronal lineages. Nonetheless, it remains controversial whether Notch activity diversifies cell fate by regulating the timing of neurogenesis or acts directly in neuronal subtype specification. Here, we address the role of Notch in the zebrafish epiphysis, a simple structure containing only two neural subtypes: projection neurons and photoreceptors. Reducing the activity of the Notch pathway results in an excess of projection neurons at the expense of photoreceptors, as well as an increase in cells retaining a mixed identity. However, although forced activation of the pathway inhibits the projection neuron fate, it does not promote photoreceptor identity. As birthdating experiments show that projection neurons and photoreceptors are born simultaneously, Notch acts directly during neuronal specification rather than by controlling the timing of neurogenesis. Finally, our data suggest that two distinct signals are required for photoreceptor fate specification: one for the induction of the photoreceptor fate and the other, involving Notch, for the inhibition of projection neuron traits. We propose a novel model in which Notch resolves mixed neural identities by repressing an undesired genetic program.