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.

Wang Y¹, Wu H¹, Fontanet P¹, Codeluppi S², Akkuratova N³, Petitpré C¹, Xue-Franzén Y¹, Niederreither K⁴, Sharma A¹, Da Silva F⁵, Comai G⁶, Agirman G¹, Palumberi D¹, Linnarsson S², Adameyko I^3,7, Moqrich A⁸, Schedl A⁵, La Manno G⁹, Hadjab S¹⁰, Lallemend F^11,12.

Author information

1. Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden.
2. Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden.
3. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 17165, Sweden.
4. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104, Inserm U964, Université de Strasbourg, Illkirch, France.
5. Université Côte d’Azur, Inserm, CNRS, iBV, 06108, Nice, France.
6. Stem Cells & Development – Institut Pasteur – CNRS UMR3738, 75015, Paris, France.
7. Center for Brain Research, Medical University Vienna, Vienna, Austria.
8. Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille (IBDM), UMR 7288, 13288, Marseille, France.
9. Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
10. Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden. saida.hadjab@ki.se.
11. Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden. francois.lallemend@ki.se.
12. Ming Wai Lau Centre for Reparative Medicine, Stockholm node, Karolinska Institutet, Stockholm, Sweden. francois.lallemend@ki.se.

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.

PMID: 31515492
DOI: 10.1038/s41467-019-12119-3