Abstract

During embryogenesis, stem cells first undergo a phase of amplification which is followed by the unfolding of differentiation programs ultimately leading to functional tissues 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 principles by which temporal patterning cooption governs the hierarchy of brain tumors. Our work illuminates the links between development, regeneration and tumorigenesis and provides a paradigm to understand cancers with developmental origins.

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