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 I3,7, Moqrich A8, Schedl A5, La Manno G9, Hadjab S10, Lallemend F11,12.
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. email@example.com.
11. Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden. firstname.lastname@example.org.
12. Ming Wai Lau Centre for Reparative Medicine, Stockholm node, Karolinska Institutet, Stockholm, Sweden. email@example.com.
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.