Genetic Regulation of Differentiation and Morphogenesis

分化和形态发生的遗传调控

• 批准号: 203656-2012
• 负责人: Godt, Dorothea
• 金额: $ 2.04万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=523507
• 关键词: Genetic; Regulation; Differentiation; Morphogenesis

The goal of my research program is to gain an understanding of molecular networks that drive cell differentiation and morphogenesis. The Traffic jam (Tj) protein is a key regulator of these processes in Drosophila gonads, which we use as a model system. Tj is a close relative of the large Maf transcription factors in mammals that have multiple roles in cell differentiation and cancer. In Drosophila gonads, where germ cells develop under the guidance of adjacent somatic cells, Tj functions in the somatic cells controlling their differentiation program and ability to interact with the germ cells. Here, I propose to focus on three Tj-dependent processes to gain further insights into the function of this Maf factor and the molecular network, in which it operates. (i) We discovered that Tj influences several factors that promote tissue invasion and cell migration in ovarian follicles. We will investigate how Tj regulates the activity of these genes, which will lead to a better understanding of a molecular circuit that contributes to invasive and migratory behaviour of cells, properties important in normal development and cancer biology. (ii) We discovered that Tj is important for the formation of the niche that sustains the stem cells from which egg and sperm originate and regulates stem cell numbers. Here, we propose to investigate the interactions between Tj and another niche regulator to better understand the mechanisms that control stem cells. (iii) How cells decide between remaining undifferentiated or moving toward differentiation is a critical question in stem cell biology. We will investigate how the balance between factors that act antagonistically on promoting and preventing cell differentiation controls early germ cell development, by studying the function of a dedifferentiation factor and how it is controlled by the differentiation factor Tj. Collectively, this research will foster our understanding of the molecular network in which the Maf transcription factor Tj operates and how it contributes to cell differentiation and morphogenesis. As Maf factors are conserved in mammals, I anticipate that our research will contribute to a more general understanding of Maf-dependent gene regulatory networks and how Mafs contribute to cell differentiation.

我的研究计划的目标是了解驱动细胞分化和形态发生的分子网络。交通堵塞(TJ)蛋白是果蝇性腺这些过程的关键调节因子，我们将其用作模型系统。TJ是哺乳动物中大的MAF转录因子的近亲，这些转录因子在细胞分化和癌症中起着多种作用。在果蝇的性腺中，生殖细胞在邻近体细胞的指导下发育，TJ在体细胞中发挥作用，控制体细胞的分化程序和与生殖细胞相互作用的能力。在这里，我建议将重点放在三个依赖于TJ的过程上，以进一步深入了解这种Maf因子的功能及其运行的分子网络。(I)我们发现TJ影响几个促进卵泡组织侵袭和细胞迁移的因素。我们将研究TJ如何调节这些基因的活性，这将导致更好地理解有助于细胞侵袭和迁移行为的分子电路，这些特性在正常发育和癌症生物学中很重要。(Ii)我们发现TJ对于维持卵子和精子来源的干细胞并调节干细胞数量的生态位的形成是重要的。在这里，我们建议研究TJ和另一个利基调控因子之间的相互作用，以更好地了解控制干细胞的机制。(Iii)细胞如何决定是保持未分化还是走向分化是干细胞生物学中的一个关键问题。我们将通过研究去分化因子的功能以及分化因子TJ如何控制它，来研究促进和阻止细胞分化的相反因素之间的平衡是如何控制早期生殖细胞发育的。总而言之，这项研究将促进我们对MAF转录因子TJ在其中发挥作用的分子网络以及它如何促进细胞分化和形态发生的理解。由于MAF因子在哺乳动物中是保守的，我预计我们的研究将有助于更全面地理解MAF依赖的基因调控网络以及MAF如何促进细胞分化。