Cell competition from development to neurodegeneration

Abstract

ABSTRACT Cell competition is a process by which suboptimal cells are eliminated to the benefit of cells with higher fitness. It is a surveillance mechanism that senses differences in the fitness status by several modes, such as expression of fitness fingerprints, survival factor uptake rate and resistance to mechanical stress. Fitness fingerprints-mediated cell competition recognizes isoforms of the transmembrane protein Flower, and translates the relative fitness of cells into distinct fates through the Flower code. Impairments in cell competition potentiate the development of diseases like cancer and ageing-related pathologies. In cancer, malignant cells acquire a supercompetitor behaviour, killing the neighbouring cells and overtaking the tissue, thus avoiding elimination. Neurodegenerative disorders affect millions of people and are characterized by cognitive decline and locomotor deficits. Alzheimer's disease is the most common form of dementia, and one of the largely studied diseases. However, the cellular processes taking place remain unclear. Drosophila melanogaster is an emerging neurodegeneration model due to its versatility as a tool for genetic studies. Research in a Drosophila Alzheimer's disease model detected fitness markers in the suboptimal and hyperactive neurons, thus establishing a link between cell competition and Alzheimer's disease. In this Review, we overview cell competition and the new insights related to neurodegenerative disorders, and discuss how research in the field might contribute to the development of new therapeutic targets for these diseases.