A cell fitness selection model for neuronal survival during development

Nat Commun. 2019 Sep 12;10(1):4137. doi: 10.1038/s41467-019-12119-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Chick Embryo
  • Core Binding Factor Alpha 3 Subunit / metabolism
  • Mice, Inbred C57BL
  • Models, Biological*
  • Proprioception / drug effects
  • Receptor, trkC / metabolism
  • Sensory Receptor Cells / cytology*
  • Sensory Receptor Cells / drug effects
  • Signal Transduction / drug effects
  • Tretinoin / pharmacology

Substances

  • Core Binding Factor Alpha 3 Subunit
  • Tretinoin
  • Receptor, trkC