Neural cell competition sculpting brain from cradle to grave

Abstract

Darwinian selection, operating within the cellular ecosystem of multicellular organisms, drives a pervasive surveillance mechanism of cell-cell competition that shapes tissue architecture and function. While cell competition eliminates suboptimal cells to ensure tissue integrity across various tissues, neuronal competition specifically sculpts neural networks to establish precise circuits for sensory, motor and cognitive functions. However, our understanding of cell competition across diverse neural cell types in both developmental and pathological contexts remains limited. Here, we review recent advances on the phenomenon, and mechanisms and potential functions of neural cell competition (NCC), ranging from neural progenitors, neurons, astrocytes and oligodendrocytes to microglia. Physiological NCC governs cellular survival, proliferation, arborization, organization, function and territorial colonization, whereas dysregulated NCC may cause neurodevelopmental disorders, accelerate aging, exacerbate neurodegenerative diseases and drive brain tumor progression. Future work that leverages cell competition mechanisms may help to improve cognition and curb diseases.