Journal
NEURON
Volume 97, Issue 5, Pages 1049-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2018.01.030
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Funding
- Del Bene laboratory Neural Circuits Development'' is part of the Laboratoire d'Excellence (LABEX) [ANR-11-LABX-0044]
- Pierre-Gilles de Gennes pour la recherche
- Fondation pour le Recherche Medicale (FRM)
- FRM postdoctoral fellowship
- Curie International PhD program
- Boehringer Ingelheim Fonds
- Fondation Berthe Fouassier (Fondation de France) [2015-00060246, 2016-00069985]
- ATIP/AVENIR program
- ERC-StG [311159]
- CNRS
- INSERM
- Institut Curie
- [ANR-II-INBS-0014]
- Agence Nationale de la Recherche (ANR) [ANR-11-LABX-0044] Funding Source: Agence Nationale de la Recherche (ANR)
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A conserved organizational and functional principle of neural networks is the segregation of axon-dendritic synaptic connections into laminae. Here we report that targeting of synaptic laminae by retinal ganglion cell (RGC) arbors in the vertebrate visual system is regulated by a signaling system relying on target-derived Reelin and VLDLR/Dab1a on the projecting neurons. Furthermore, we find that Reelin is distributed as a gradient on the target tissue and stabilized by heparan sulfate proteoglycans (HSPGs) in the extracellular matrix (ECM). Through genetic manipulations, we show that this Reelin gradient is important for laminar targeting and that it is attractive for RGC axons. Finally, we suggest a comprehensive model of synaptic lamina formation in which attractive Reelin counter-balances repulsive Slit1, thereby guiding RGC axons toward single synaptic laminae. We establish a mechanism that may represent a general principle for neural network assembly in vertebrate species and across different brain areas.
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