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© Research
Publication : Nature communications

A cell fitness selection model for neuronal survival during development.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 12 Sep 2019

Wang Y, Wu H, Fontanet P, Codeluppi S, Akkuratova N, Petitpré C, Xue-Franzén Y, Niederreither K, Sharma A, Da Silva F, Comai G, Agirman G, Palumberi D, Linnarsson S, Adameyko I, Moqrich A, Schedl A, La Manno G, Hadjab S, Lallemend F,

Link to Pubmed [PMID] – 31515492

Link to DOI – 10.1038/s41467-019-12119-3

Nat Commun 2019 09; 10(1): 4137

Developmental cell death plays an important role in the construction of functional neural circuits. In vertebrates, 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 retinoic acid and transcription factors, and are independent of the target and neurotrophins. These molecular features are genetically encoded, representing two distinct subgroups of neurons with contrasted functional maturation states and survival outcome. Thus, in this model, a heterogeneous code of intrinsic cell fitness in neighboring neurons provides differential competitive advantage resulting in the selection of cells with higher capacity to survive and functionally integrate into neural networks.