Genetic Regulation of Differentiation and Morphogenesis

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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.