Genetic Regulation of Differentiation and Morphogenesis

我的研究计划的目标是获得驱动细胞分化和形态发生的分子网络的理解。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Maf转录因子的近亲，其在细胞分化和癌症中具有多种作用。在果蝇性腺中，生殖细胞在相邻体细胞的指导下发育，Tj在体细胞中起作用，控制其分化程序和与生殖细胞相互作用的能力。在这里，我建议专注于三个Tj依赖的过程，以获得进一步的见解，这个Maf因子的功能和分子网络，它的运作。(i)我们发现Tj影响促进卵泡中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，这将有助于更好地了解有助于细胞侵袭和迁移行为的分子回路，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的生态位的形成和调节干细胞数量是重要的。在这里，我们建议调查Tj和另一个小生境调节器之间的相互作用，以更好地了解控制干细胞的机制。(iii)细胞如何在保持未分化或向分化方向发展之间做出决定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它如何受分化因子Tj的控制，来研究对促进和阻止细胞分化起拮抗作用的因子之间的平衡如何控制早期生殖细胞发育。总的来说，这项研究将促进我们对Maf转录因子Tj运作的分子网络以及它如何有助于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.