Genetic Regulation of Differentiation and Morphogenesis

我的研究项目的目标是了解驱动细胞分化和形态发生的分子网络。交通堵塞蛋白（Tj）是果蝇性腺中这些过程的关键调节器，我们将其作为模型系统。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，生殖细胞在邻近体细胞的引导下发育，Tj在体细胞中起着控制其分化程序和与生殖细胞相互作用的能力的作用。在这里，我建议将重点放在三个tj依赖的过程上，以进一步了解该Maf因子的功能及其运作的分子网络。(i)我们发现Tj影响卵巢卵泡中促进组织侵袭和细胞迁移的几个因素。我们将研究Tj如何调节这些基因的活性，这将有助于更好地理解有助于细胞侵袭和迁移行为的分子回路，以及正常发育和癌症生物学中重要的特性。（ii）我们发现Tj对于维持卵子和精子起源的干细胞和调节干细胞数量的生态位的形成很重要。在这里，我们建议研究Tj和另一个小生境调节因子之间的相互作用，以更好地了解控制干细胞的机制。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及其如何受分化因子Tj的控制，来研究促进和阻止细胞分化的拮抗因子之间的平衡如何控制早期生殖细胞的发育。总的来说，这项研究将促进我们对Maf转录因子Tj的分子网络的理解，以及它如何促进细胞分化和形态发生。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Maf依赖的基因调控网络以及Maf如何促进细胞分化。

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.