Studies on the neurotrophic factor Manf and the pleiotropic factor Lin-28 during Drosophila development
Year: 2014
Type: dissertation
Abstract: Developmental biology studies how a single cell will give rise to a fully developed, highly ordered and reproducible living organism. In order for this to occur, the fertilized egg needs to grow, divide and differentiate to produce different cell types. Subsequently, these different cell types need to organize into predefined arrays of committed cell groups to produce specialized tissues and organs, which constitute the living multicellular organism. Although the final product seems enormously complex, the multicellular organism is composed of cells that they all have the same set of genes. Cells differentiate by switching on and off the expression of different molecules and they produce and respond to signals which result in cells growing, dividing and dying in a strict spatiotemporal manner. In this work I aimed to address questions on the molecular mechanisms during development by using the fruit fly Drosophila melanogaster as a model system. The first aim of my studies was to characterize and investigate the role of Manf during Drosophila pupation and adulthood. MANF is an evolutionarily conserved neurotrophic factor, which has previously been reported to protect and restore dopaminergic neurons in mammals. In Drosophila embryos DmMANF has been shown to be specifically expressed in glial populations, while DmMANF null mutants die early during development while they exhibit specific and significant reduction of dopaminergic neurites. Our data reveal that in pupae and adults, DmMANF has a much wider expression pattern and it is localized both in glia and neurons. This analysis led to the identification of an unusual phenotype in the Drosophila pupal brain. We showed when Manf is silenced, or either autophagy or immunity is induced in glia, macrophage-like cells appear in areas of the pupal brain that are normally devoid of cell bodies. We identified molecular markers and pathways that are activated in these cells, as well as some of the unique subcellular features they possess. This study brings new and elegant data in several aspects of glial biology with exciting perspectives for studying brain plasticity and repair. The second project was to characterize the expression of Gfrl receptor, the Drosophila homolog of the mammalian GFRα receptor in the Drosophila adult brain. The results showed that although the Gfrl receptor is widely expressed in the fly adult brain, this expression is in surprising contrast to the missing expression of dRet, the Drosophila Ret homolog. This data provide novel insights into further elucidation of the Ret-dependent and Ret-independent -GFRα signaling complexes, as well as to further understand the several aspects of invertebrate brain development and function. The third aim of this study was to investigate the role of the conserved pleiotropic factor Lin28 during Drosophila development. Previous studies have shown that Lin28 is one of the factors sufficient to reprogram human somatic cells into induced pluripotent stem cells. By constructing Lin-28 null mutants, our data reveal that Lin-28 mutant files were viable but sub-fertile, exhibiting oogenesis defects. These results will help us improve our understanding of Lin28 role in stem cell maintenance and differentiation.
Source: Työväentutkimus Vuosikirja
Author: Vassilis Stratoulias
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1497078306