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The role of the E2F transcription factors in regulating stem cell functions during Arabidopsis root development

E2F转录因子在拟南芥根发育过程中调节干细胞功能的作用

基本信息

批准号：
BB/D017599/1
负责人：
Laszlo Bogre
金额：
$ 45.52万
依托单位：
Royal Holloway University of London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2006
资助国家：
英国
起止时间：
2006 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FD017599%2F1
关键词：
role E2F transcription factors regulating

项目摘要

Plants form organs, grow and develop throughout their lifetime, which can be over a thousand years in the case of some trees. For that purpose they maintain pluripotent somatic stem cells within the meristems, local pools of mitotically active cells. In roots these stem cells surround the mitotically less active organising centre, called the quiescent centre (QC) and together they form a stem cell niche. The quiescent centre is specified by combinatorial action of two gene sets. The PLETHORA genes are transcribed in response to the phytohormone, auxin accumulation and are required to position QC basal in roots while an independent developmental pathway of the genes named after the mutants, SCARECROW (SCR) and SHORT-ROOT (SHR), sets up the radial position for QC. Although we are beginning to understand the patterning in meristems, we do not know the mechanisms that keep cells undifferentiated around the region of QC and what sets up the field of differentiation as cells leave the meristematic zone. Auxin has long been known to be essential for cell division in culture and to be involved in a wide range of developmental processes including the maintenance and initiation of organs that depend on the regulation of the balance between cell division and differentiation. Channels are carefully positioned and regulated to allow auxin to get in and out from cells and to determine the directionality of auxin flow from cell to cell that leads to the formation of highly dynamic fields of auxin gradients. The idea is, that cells are able to distinguish these different auxin concentrations and respond to them differently, for instance by growth through elongation or by cell division, but the exact mechanism is not known. We know however, that different auxin concentrations are sensed by a protein known as TIR1, which is able to operate sophisticated switches on large sets of genes that rely on lifting repressor molecules by auxin-regulated protein degradation. Recently we have discovered two transcriptional regulators in cell division with antagonistic roles, one called E2Fb promotes cell proliferation and co-ordinates it with cell growth; while the other, called E2Fc, blocks cell division, and promote cells to attain specific functions, termed cell differentiation. We were surprised to find that the abundance of these proteins are oppositely regulated by auxin, E2Fb being stabilised while E2Fc is destabilised. We formulated a working hypothesis that auxin concentrations are converted into opposing concentration gradients of these positive and negative cell cycle regulators and constitute the switch between decisions to divide or elongate and differentiate. E2Fs are kept under control by the pocket protein called retinoblastoma (RB), because it was discovered in animals to cause uncontrolled tumour growth in the eye. It was recently discovered that in Arabidopsis an RB related protein is essential to maintain the stem cell niche in roots in response to the developmental regulator SCARECROW. Thus, E2Fs provide a converging point for developmental regulators and auxin to determine stem cell functions. We propose to test this model genetically by observing the phenotypes of mutants in E2F genes in combination with the RB related gene and mutants in regulators of auxin production or transport. We also plan to visualise the E2F protein distribution in relation to auxin gradients. Because E2Fs operate by controlling large number of genes, it is vital that we identify the genes E2Fs bind to and determine how these genes are regulated. Our work should uncover how auxin regulates cell division, and thus plant growth.

植物在其一生中形成器官，生长和发育，在某些树木的情况下可以超过一千年。为了这个目的，它们在分生组织内维持多能性体干细胞，分生组织是有丝分裂活性细胞的局部库。在根中，这些干细胞围绕着有丝分裂不太活跃的组织中心，称为静止中心（QC），它们一起形成干细胞龛。静止中心由两个基因组的组合作用指定。PLETHORA基因响应于植物激素、生长素积累而转录，并且需要将QC定位在根部基部，而以突变体SCARECROW（SCR）和SHORT-ROOT（SHR）命名的基因的独立发育途径为QC设置径向位置。虽然我们开始了解分生组织中的模式，但我们不知道QC区域周围细胞未分化的机制，以及当细胞离开分生组织区时，是什么建立了分化场。生长素长期以来被认为是培养中细胞分裂所必需的，并且参与广泛的发育过程，包括依赖于细胞分裂和分化之间平衡的调节的器官的维持和启动。通道被仔细定位和调节，以允许生长素进出细胞，并确定生长素从细胞到细胞流动的方向性，从而形成高度动态的生长素梯度场。这个想法是，细胞能够区分这些不同的生长素浓度，并对它们做出不同的反应，例如通过伸长或细胞分裂生长，但确切的机制尚不清楚。然而，我们知道，不同的生长素浓度是由一种称为TIR 1的蛋白质感知的，该蛋白质能够在大量基因上操作复杂的开关，这些基因依赖于通过生长素调节的蛋白质降解来解除阻遏物分子。最近我们发现了两种在细胞分裂中具有拮抗作用的转录调节因子，一种称为E2 Fb，促进细胞增殖并协调细胞生长;另一种称为E2 Fc，阻断细胞分裂，促进细胞获得特定功能，称为细胞分化。我们惊讶地发现，这些蛋白质的丰度受到生长素的相反调节，E2 Fb被稳定化，而E2 Fc不稳定。我们制定了一个工作假设，生长素浓度转化为这些积极和消极的细胞周期调节相反的浓度梯度，并构成了决定之间的开关，分裂或延长和分化。E2 F由称为视网膜母细胞瘤（RB）的口袋蛋白控制，因为它在动物中被发现会导致眼睛中不受控制的肿瘤生长。最近发现，在拟南芥中，RB相关蛋白是维持根中的干细胞生态位响应于发育调节剂SCARECROW所必需的。因此，E2 Fs为发育调节因子和生长素提供了确定干细胞功能的汇合点。我们建议通过观察E2 F基因突变体与RB相关基因和生长素生产或运输调节剂突变体的表型来遗传地测试该模型。我们还计划可视化E2 F蛋白分布与生长素梯度的关系。由于E2 Fs通过控制大量基因来发挥作用，因此我们必须确定E2 Fs结合的基因并确定这些基因是如何调节的。我们的工作应该揭示生长素如何调节细胞分裂，从而调节植物生长。