WT1 regulates the development of the posterior taste field
WT1 regulates the development of the posterior taste field
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DOI：
10.1242/dev.105676
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发表时间：
2014-06-01
期刊：
影响因子：
4.6
通讯作者：
Medler, Kathryn F.
中科院分区：
文献类型：
--
作者：
Gao, Yankun;Toska, Eneda;Medler, Kathryn F.
尽管味觉在决定营养摄入方面很重要，但我们对控制外周味觉系统发育的过程的理解还很缺乏。已经确定了几种味觉发育的早期调节因子，包括sonic hedgehog， bone morphogenetic protein 4和Wnt/ β -catenin信号通路的多个成员。然而，这些因素的调节，包括它们的诱导，仍然知之甚少。在这里，我们确定了Wilms肿瘤1蛋白（WT1）在环valvalate （CV）乳头发育中的关键作用。WT1是一种转录因子，在包括嗅觉和视觉系统在内的多种组织的正常发育中都很重要。在小鼠中，当CV味觉基因开始形成时，WT1的表达可通过E12.5检测到。在缺乏WT1的小鼠中，CV不能正常发育，与野生型相比，早期味觉发育的标志物失调。我们证明WT1靶基因Lef1、Ptch1和Bmp4的表达在WT1敲除小鼠的发育舌头组织中显著降低，并且在正常舌头中，WT1与这些基因的启动子区域结合。此外，在培养的味觉细胞中，siRNA敲低WT1会导致Lef1和Ptch1的表达减少。我们的数据表明，WT1通过调节多种信号通路在味觉基板的形成和模式中发挥作用，在CV的发展中是一个至关重要的转录因子。
Despite the importance of taste in determining nutrient intake, our understanding of the processes that control the development of the peripheral taste system is lacking. Several early regulators of taste development have been identified, including sonic hedgehog, bone morphogenetic protein 4 and multiple members of the Wnt/beta-catenin signaling pathway. However, the regulation of these factors, including their induction, remains poorly understood. Here, we identify a crucial role for the Wilms' tumor 1 protein (WT1) in circumvallate (CV) papillae development. WT1 is a transcription factor that is important in the normal development of multiple tissues, including both the olfactory and visual systems. In mice, WT1 expression is detectable by E12.5, when the CV taste placode begins to form. In mice lacking WT1, the CV fails to develop normally and markers of early taste development are dysregulated compared with wild type. We demonstrate that expression of the WT1 target genes Lef1, Ptch1 and Bmp4 is significantly reduced in developing tongue tissue derived from Wt1 knockout mice and that, in normal tongue, WT1 is bound to the promoter regions of these genes. Moreover, siRNA knockdown of WT1 in cultured taste cells leads to a reduction in the expression of Lef1 and Ptch1. Our data identify WT1 as a crucial transcription factor in the development of the CV through the regulation of multiple signaling pathways that have established roles in the formation and patterning of taste placodes.