Angela GIANGRANDE
Nervous and immune system development
Nervous and immune system development
KEYWORDS: Stem Cell,
Nervous System, Hematopoiesis
Drosophila
Fate determinants
Evolution
Nervous System, Hematopoiesis
Drosophila
Fate determinants
Evolution
A major challenge in modern biology is to understand how cell diversity is generated from multipotent precursors and how cells interact to build the sophisticated metazoan architecture. In humans, defects in these processes lead to severe pathologies, from mental retardation to cancer. Evolutionary conservation, sophisticated genetics and simple organization make Drosophila melanogaster an ideal animal model to study these events in vivo and in vitro, at cellular resolution. Moreover, stem cells have been identified in several tissues of the developing and adult fly and the underlying molecular cascades have been thoroughly analyzed.
The nervous system constitutes one of the most complex tissues, made of neurons and glia of different types. These cells arise from multipotent precursors or stem cells and our goal is to study the molecular and the epigenetic events controlling cell differentiation and reprogramming. We have found that such multipotent precursors can be reprogrammed but loose this plastic feature during development. We have identified the molecular pathway that drives the fate choice neurons and glia and have shown that a single transcription factor is necessary and sufficient to promote gliogenesis in Drosophila. This factor also induces a glia-specific epigenetic signature. We are characterizing its role and mode of action of the glial determinant as well as the bases of the cell-specific epigenetic features.
Interestingly, the same transcription factor that triggers gliogenesis in flies is also necessary in the embryonic blood cells that specifically originate from primitive hematopoiesis, showing that cell-specific transcriptional and epigenetic landscapes bias the activity of fate determinants. We are currently analyzing how does a potent transcription factor controls specific fates in cells of different layers, ectoderm for glia, mesoderm for blood cells.
Finally, fly hematopoiesis occurs in primitive and definitive waves similar to what has been observed in vertebrates. One of the most exciting findings in the field is that each hematopoietic wave seems to have specific functions, changing our view on the development and mode of action of the immune system. We can now address the molecular and cellular pathways that are wave-specific, identify the possible interactions between the hematopoietic waves and hopefully analyze their evolutionary conservation.
The nervous system constitutes one of the most complex tissues, made of neurons and glia of different types. These cells arise from multipotent precursors or stem cells and our goal is to study the molecular and the epigenetic events controlling cell differentiation and reprogramming. We have found that such multipotent precursors can be reprogrammed but loose this plastic feature during development. We have identified the molecular pathway that drives the fate choice neurons and glia and have shown that a single transcription factor is necessary and sufficient to promote gliogenesis in Drosophila. This factor also induces a glia-specific epigenetic signature. We are characterizing its role and mode of action of the glial determinant as well as the bases of the cell-specific epigenetic features.
Interestingly, the same transcription factor that triggers gliogenesis in flies is also necessary in the embryonic blood cells that specifically originate from primitive hematopoiesis, showing that cell-specific transcriptional and epigenetic landscapes bias the activity of fate determinants. We are currently analyzing how does a potent transcription factor controls specific fates in cells of different layers, ectoderm for glia, mesoderm for blood cells.
Finally, fly hematopoiesis occurs in primitive and definitive waves similar to what has been observed in vertebrates. One of the most exciting findings in the field is that each hematopoietic wave seems to have specific functions, changing our view on the development and mode of action of the immune system. We can now address the molecular and cellular pathways that are wave-specific, identify the possible interactions between the hematopoietic waves and hopefully analyze their evolutionary conservation.