A cell fitness selection model for neuronal survival during development

Developmental cell death plays an important role in the construction of functional neural circuits. In vertebrate, the canonical view proposes a selection of the surviving neurons through stochastic competition for target-derived neurotrophic signals, implying an equal potential for neurons to compete. Here we show an alternative cell fitness selection of neurons that is defined by a specific neuronal heterogeneity code. Proprioceptive sensory neurons that will undergo cell death and those that will survive exhibit different molecular signatures that are regulated by the retinoic acid and transcription factors, and are independent of neurotrophins and of the target. These molecular features are genetically encoded, representing two distinct subgroups of neurons with contrasted survival outcome and functional maturation states. Thus, in our model, a heterogeneous code of intrinsic cell fitness in neighboring neurons provides differential competitive advantage resulting in the selection of cells with higher intrinsic capacity to survive and to functionally integrate into neural networks. In total 2 samples (dorsal root ganglia dissociated single neurons at E11.5 and E12.5) were collected.