Retinoblastoma family protein promotes normal R8-photoreceptor differentiation in the absence of rhinoceros by inhibiting dE2F1 activity.
Retinoblastoma family protein promotes normal R8-photoreceptor differentiation in the absence of rhinoceros by inhibiting dE2F1 activity.
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DOI：
10.1016/j.ydbio.2009.09.004
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发表时间：
2009-11-01
影响因子：
2.7
通讯作者：
Du, Wei
中科院分区：
文献类型：
--
作者：
Steele, Latishya;Sukhanova, Madina J.;Xu, Jinhua;Gordon, Gabriel M.;Huang, Yongsheng;Yu, Long;Du, Wei
视网膜母细胞瘤基因Rb是果蝇中保守的肿瘤抑制基因原型。虽然我们对Rb在细胞增殖和凋亡中的作用了解甚多，但对Rb如何调节细胞分化却知之甚少。果蝇Rb （Drosophila Rb, rbf）的失活表现出与小鼠Rb失活相似的细微分化缺陷，提示在细胞分化控制中存在冗余机制。为了测试这种可能性，并表征Rbf在视网膜发育过程中细胞分化中的作用，我们进行了遗传筛选，并在犀牛（rno）中发现了一个突变，该突变导致协同分化缺陷，同时Rbf失活。对早期分化缺陷多r8表型的表征表明，这种表型是由于Notch配体Delta （Dl）的表达减少导致Notch信号的数量有限造成的。降低Dl基因剂量可增强多重r8表型，而增加Dl基因剂量可抑制多重r8表型。有趣的是，去除dE2F1的转录激活可以部分恢复rbf、rno突变克隆中的Dl表达，并抑制相关的分化缺陷，这表明rbf的这种分化功能是通过其对dE2F1活性的调节来介导的。
The retinoblastoma gene Rb is a prototype tumor suppressor which is conserved in Drosophila. Although much is known about the roles of Rb in cell proliferation and apoptosis, much less is known about how Rb regulates cell differentiation. Inactivation of Drosophila Rb (rbf) exhibited subtle differentiation defects similar to inactivation of Rb in mice, suggesting the existence of redundant mechanisms in the control of cell differentiation. To test this possibility and to characterize the role of Rbf in cell differentiation during retinal development, we carried out a genetic screen and identified a mutation in rhinoceros (rno), which leads to synergistic differentiation defects in conjunction with rbf inactivation. Characterization of an early differentiation defect, the multiple-R8 phenotype, revealed that this phenotype was caused by limiting amounts of Notch signaling due to reduced expression of the Notch ligand, Delta (Dl). Decreasing the gene dosage of Dl enhanced the multiple-R8 phenotype, while increasing the level of Dl suppressed this phenotype. Interestingly, removal of the transcriptional activation of dE2F1 partially restores Dl expression in rbf,rno mutant clones and suppresses the associated differentiation defects, indicating that this differentiation function of RBF is mediated by its regulation of dE2F1 activity.
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影响因子：
64.5
作者：
GU, W;SCHNEIDER, JW;NADALGINARD, B
通讯作者：
NADALGINARD, B
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