Pax2 and Pea3 synergize to activate a novel regulatory enhancer for spalt4 in the developing ear
Pax2 and Pea3 synergize to activate a novel regulatory enhancer for spalt4 in the developing ear
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DOI：
10.1016/j.ydbio.2009.11.004
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发表时间：
2010-04-15
影响因子：
2.7
通讯作者：
Bronner-Fraser, Marianne
中科院分区：
文献类型：
--
作者：
Barembaum, Meyer;Bronner-Fraser, Marianne
转录因子 spalt4 是耳基板诱导中的关键早期反应基因。在这里，我们描述了 spalt4 的顺式调控区域，负责激活其在发育中的耳基板中的表达，并报告了一种新型核心增强子的分离。对假定的转录因子结合位点的鉴定和突变分析表明，FGF 信号传导的下游效应子 Pea3 和 Pax2 在耳朵发育过程中直接激活 spalt4。吗啡啉介导的每个因子的敲低会减少或消除报告基因的表达。相比之下，Pea3 和 Pax2 的联合过度表达会驱动异位报告基因表达，表明它们具有协同作用。这些研究通过鉴定介导 spalt4 表达的直接输入，扩展了早期耳发育的基因调控网络。 (C) 2009 Elsevier Inc. 保留所有权利。
The transcription factor spalt4 is a key early-response gene in otic placode induction. Here, we characterize the cis-regulatory regions of spalt4 responsible for activation of its expression in the developing otic placode and report the isolation of a novel core enhancer. Identification and mutational analysis of putative transcription factor binding sites reveal that Pea3, a downstream effector of FGF signaling, and Pax2 directly activate spalt4 during ear development. Morpholino-mediated knock-down of each factor reduces or eliminates reporter expression. In contrast, combined over-expression of Pea3 and Pax2 drives ectopic reporter expression, suggesting that they function synergistically. These studies expand the gene regulatory network underlying early otic development by identifying direct inputs that mediate spalt4 expression. (C) 2009 Elsevier Inc. All rights reserved.