Principles of lineage progression during development and tumorigenesis

Principles of lineage progression during development and tumorigenesis

Dr Cédric Maurange; Developmental Biology Institute of Marseille, CNRS

2023-2024 : Overseas fellow at Churchill College, Cambridge 2009-present : CNRS Researcher (DR1). Group leader of the Neural Stem Cell Plasticity team at the Developmental Biology Institute of Marseille (IBDM/CNRS UMR7288), 2003-2009 : Post-doc with Dr. Alex Gould. Department of Developmental Neurobiology. MRC National Institute for Medical Research (Mill Hill, London, UK). 1998-2002 : PhD with Prof. Renato Paro. Center of Molecular Biology of Heidelberg (ZMBH), University of Heidelberg, Germany.

During embryogenesis, each stem cell first undergoes a phase of amplification which is followed by the unfolding of differentiation programs ultimately leading to a complex lineage with the correct number and diversity of cell types. The mechanisms regulating the temporality of these different phases is not fully understood. Over the last decade, studies have revealed in Drosophila an overarching temporal patterning system that schedules the different phases of stem cell/progenitor self-renewal and differentiation. I will describe how we have unveiled key players in this temporal patterning system and how they are regulated by different humoral, local or cell-intrinsic timing signals. I will also discuss our finding that temporal patterning delineates windows of malignant susceptibility in the developing brain and how its perturbation drives tumorigenesis upon various genetic insults. Finally, I will show how, using a combination of image analysis and computer simulations, we try to decipher the mechanisms by which temporal patterning cooption governs the hierarchy of brain tumors. Our work sheds light on the links between development, regeneration and tumorigenesis, and provides a paradigm for understanding how disruption of lineage progression triggers cancers with developmental origins.

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