Regulation of temporal identity transitions in Drosophila neuroblasts
Regulation of temporal identity transitions in Drosophila neuroblasts
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DOI：
10.1016/j.devcel.2004.11.019
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发表时间：
2005-02-01
影响因子：
11.8
通讯作者：
Doe, CQ
中科院分区：
文献类型：
--
作者：
Grosskortenhaus, R;Pearson, BJ;Doe, CQ
时间模式是胚胎发育的一个重要方面，但其潜在的分子机制还不是很清楚。果蝇神经母细胞是研究时间同一性的一个很好的模型：它们顺序表达四个基因(驼背-->；kruppel-->；pdm1-->；Castor)，它们的时间调节对于产生神经元多样性是必不可少的。在这里，我们表明驼背-->；Kruppel的时机是转录调控的，需要神经母细胞胞质分裂，这与神经母细胞分裂期间转录调节因子的不对称划分或来自神经母细胞后代的反馈信号一致。令人惊讶的是，Kruppel-->；pdm1-->；蓖麻计时通常发生在孤立的或G(2)受阻的神经母细胞中，因此涉及神经母细胞内在计时器。最后，我们发现驼背能够有效地调节神经母细胞的时间认同计时器：长时间的驼背表达使神经母细胞在多个分裂中保持年轻，随后的下调允许恢复Kruppel-->；pdm1-->；蓖麻的表达和正常的神经母细胞谱系。我们得出结论，有两个不同的“计时器”调节神经母细胞基因的表达：一个是需要胞质分裂的驼背-->；Kruppel计时器，另一个是独立于细胞周期的Kruppel-->；计时器。
Temporal patterning is an important aspect of embryonic development, but the underlying molecular mechanisms are not well understood. Drosophila neuroblasts are an excellent model for studying temporal identity: they sequentially express four genes (hunchback --> Kruppel --> pdm1 --> castor) whose temporal regulation is essential for generating neuronal diversity. Here we show that hunchback --> Kruppel timing is regulated transcriptionally and requires neuroblast cytokinesis, consistent with asymmetric partitioning of transcriptional regulators during neuroblast division or feedback signaling from the neuroblast progeny. Surprisingly, Kruppel --> pdm1 --> castor timing occurs normally in isolated or G(2)-arrested neuroblasts, and thus involves a neuroblast-intrinsic timer. Finally, we find that Hunchback potently regulates the neuroblast temporal identity timer: prolonged Hunchback expression keeps the neuroblast "young" for multiple divisions, and subsequent downregulation allows resumption of Kruppel --> pdm1 --> castor expression and the normal neuroblast lineage. We conclude that two distinct "timers" regulate neuroblast gene expression: a hunchback --> Kruppel timer requiring cytokinesis, and a Kruppel --> pdm1 --> castor timer which is cell cycle independent.