Zfp423/OAZ participates in a developmental switch during olfactory neurogenesis
Zfp423/OAZ participates in a developmental switch during olfactory neurogenesis
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DOI：
10.1016/j.neuron.2007.04.029
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发表时间：
2007-05-24
期刊：
影响因子：
16.2
通讯作者：
Reed, Randall R.
中科院分区：
文献类型：
--
作者：
Cheng, Li E.;Reed, Randall R.
基因表达的协调对于细胞分化和随后组织功能的建立至关重要。我们在此表明，多锌指转录因子 Zfp423/OAZ 在新分化的嗅觉受体神经元 (ORN) 中瞬时表达，并在协调未成熟和成熟阶段特异性基因的表达中发挥关键作用。小鼠中的 OAZ 缺失会损害 ORN 分化的各个方面，特别是轴突投射到嗅球的模式。 OAZ 功能获得实验表明，在 ORN 成熟过程中持续表达 OAZ 可将 ORN 发育抑制在未成熟阶段，并改变 OR 基因表达。重要的是，在成熟 ORN 中重新引入 OAZ 表达会抑制成熟标记的表达并重新激活未成熟的特异性标记。总之，这些实验表明 OAZ 参与调节 ORN 从分化到成熟的转变的发育开关。
The coordination of gene expression is critical for cell differentiation and the subsequent establishment of tissue function. We show here that a multiple zinc finger transcription factor, Zfp423/OAZ, is transiently expressed in newly differentiating olfactory-receptor neurons (ORNs) and has a key role in coordinating the expression of immature and mature stage-specific genes. OAZ deletion in mice impairs aspects of ORN differentiation, particularly the patterns of axonal projection to the olfactory bulb. OAZ gain-of-function experiments show that sustained OAZ expression throughout ORN maturation arrests ORN development at an immature stage and alters OR gene expression. Importantly, reintroducing OAZ expression in mature ORNs suppresses mature marker expression and reactivates immature-specific markers. Together, these experiments suggest that OAZ participates in a developmental switch regulating the transition from differentiation to maturation in ORNs.