Genetic mechanisms of differentiation and morphogenesis

我的研究计划的目标是了解驱动细胞分化和行为并定义组织的形状和结构的分子网络。交通堵塞 (Tj) 蛋白是果蝇性腺中这些过程的关键调节因子，我们将其用作模型系统。 Tj 是哺乳动物中大型 Maf 转录因子的近亲，在细胞分化和癌症中发挥多种作用。在果蝇性腺中，生殖细胞在相邻体细胞的指导下发育，Tj 在体细胞中发挥作用，控制其分化程序以及彼此之间以及与生殖细胞正确相互作用的能力。 Here, I propose to focus on two Tj-dependent processes to further elucidate its function in regulating the morphogenetic behaviour of cells. (i) The stem cells in the gonads from which egg and sperm originate are sustained by a somatic niche. We discovered that Tj is essential for the formation of this niche.在这里，我们建议识别和分析在 Tj 控制下控制不同体细胞生态位细胞的发育和空间排列的因素。 (ii) 细胞迁移在正常发育和癌症中发挥着重要作用，并由基于肌动蛋白的细胞突起驱动。我们发现 Tj 控制卵泡中的细胞迁移，并将蛋白激酶 C δ (Pkc) 确定为 Tj 的潜在靶点。 Tj 和 Pkcd 似乎都调节细胞突起中丝状肌动蛋白的结构。在这里，我们建议研究 Pkc 在细胞迁移过程中调节肌动蛋白细胞骨架的功能及其与其他肌动蛋白调节因子的相互作用。总的来说，这项研究将促进我们对 Maf 转录因子 Tj 下游运作并调节细胞行为的分子网络的理解，从而促进细胞迁移和三维组织组织。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了解指导组织发育的 Maf 依赖性过程。 **

The goal of my research program is to gain an understanding of molecular networks that drive cell differentiation and behaviour and define the shape and structure of tissues. 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 properly interact with each other and with the germ cells. Here, I propose to focus on two Tj-dependent processes to further elucidate its function in regulating the morphogenetic behaviour of cells. (i) The stem cells in the gonads from which egg and sperm originate are sustained by a somatic niche. We discovered that Tj is essential for the formation of this niche. Here, we propose to identify and analyze the factors that control the development and spatial arrangement of the different somatic niche cells under the control of Tj. (ii) Cell migration plays an important role in normal development and cancer and is driven by actin-based cellular protrusions. We discovered that Tj controls cell migration in ovarian follicles and identified Protein kinase C delta (Pkc) as a potential target of Tj. Both Tj and Pkcd seem to regulate the structure of filamentous actin in cellular protrusions. Here, we propose to investigate the function of Pkc in regulating the actin cytoskeleton during cell migration and its interactions with other actin regulators. Collectively, this research will foster our understanding of the molecular network that operates downstream of the Maf transcription factor Tj and regulates the behaviour of cells contributing to cell migration and three-dimensional tissue organization. As Maf factors are conserved in mammals, I anticipate that our research will contribute to a more general understanding of Maf-dependent processes that guide tissue development.**