Prospero and Pax2 combinatorially control neural cell fate decisions by modulating Ras- and Notch-dependent signaling.
Prospero and Pax2 combinatorially control neural cell fate decisions by modulating Ras- and Notch-dependent signaling.
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DOI：
10.1186/1749-8104-6-20
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发表时间：
2011-05-03
影响因子：
3.6
通讯作者：
Cook T
中科院分区：
文献类型：
--
作者：
Charlton-Perkins M;Whitaker SL;Fei Y;Xie B;Li-Kroeger D;Gebelein B;Cook T
等价群的概念，即具有相同潜能的细胞群，可以作为理解神经细胞类型特化的有用范例。在果蝇的眼睛中，一组五个细胞，称为“R7等效组”，产生一个感光神经元和四个晶状体分泌上皮细胞。神经元与非神经元细胞命运之间的这种选择取决于Notch/Delta-和Ras/促分裂原活化蛋白激酶（MAPK）-依赖性信号传导途径的不同要求和之间的串扰。然而，这两条信号通路的下游事件如何介导不同的细胞命运决定，仍有许多问题没有得到解答。在这里，我们证明了Ras和Notch信号传导的两个直接下游靶点，转录因子Prospero和dPax 2，是R7等效组中神经元与非神经元细胞命运决定的重要调节因子。Prospero控制神经元命运所需的高活化MAPK水平，而dPax 2抑制Delta表达以防止神经元命运。重要的是，这两种因子的活性是正确的细胞命运决定所必需的。这些数据表明，Ras和Notch信号传导通过Pros和dPax 2的组合和相反活性在R7等效组内的细胞命运决定期间被整合。我们的研究提供了一个第一个例子，两个独立的转录因子的差异表达和协同作用如何决定细胞的命运在一个等价组。由于Ras和Notch信号的整合与许多发育和癌症模型相关，这些发现应该为细胞特异性如何在不同的生物学背景下通过普遍使用的信号通路实现提供新的见解。
The concept of an equivalence group, a cluster of cells with equal potential to adopt the same specific fate, has served as a useful paradigm to understand neural cell type specification. In the Drosophila eye, a set of five cells, called the 'R7 equivalence group', generates a single photoreceptor neuron and four lens-secreting epithelial cells. This choice between neuronal versus non-neuronal cell fates rests on differential requirements for, and cross-talk between, Notch/Delta- and Ras/mitogen-activated protein kinase (MAPK)-dependent signaling pathways. However, many questions remain unanswered related to how downstream events of these two signaling pathways mediate distinct cell fate decisions. Here, we demonstrate that two direct downstream targets of Ras and Notch signaling, the transcription factors Prospero and dPax2, are essential regulators of neuronal versus non-neuronal cell fate decisions in the R7 equivalence group. Prospero controls high activated MAPK levels required for neuronal fate, whereas dPax2 represses Delta expression to prevent neuronal fate. Importantly, activity from both factors is required for proper cell fate decisions to occur. These data demonstrate that Ras and Notch signaling are integrated during cell fate decisions within the R7 equivalence group through the combinatorial and opposing activities of Pros and dPax2. Our study provides one of the first examples of how the differential expression and synergistic roles of two independent transcription factors determine cell fate within an equivalence group. Since the integration of Ras and Notch signaling is associated with many developmental and cancer models, these findings should provide new insights into how cell specificity is achieved by ubiquitously used signaling pathways in diverse biological contexts.
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影响因子：
64.8
作者：
FORTINI, ME;SIMON, MA;RUBIN, GM
通讯作者：
RUBIN, GM
影响因子：
10.5
作者：
Fu, WM;Noll, M
通讯作者：
Noll, M
影响因子：
5.6
作者：
Gokden, Neriman;Gokden, Murat;MeKenney, Jesse K.
通讯作者：
MeKenney, Jesse K.
DOI：
10.1073/pnas.86.16.6245
发表时间：
1989-08-01
影响因子：
11.1
作者：
BOWTELL, DDL;KIMMEL, BE;RUBIN, GM
通讯作者：
RUBIN, GM
影响因子：
64.5
作者：
BASLER, K;CHRISTEN, B;HAFEN, E
通讯作者：
HAFEN, E