ZFIN ID: ZDB-PUB-180214-4
An Attractive Reelin Gradient Establishes Synaptic Lamination in the Vertebrate Visual System
Di Donato, V., De Santis, F., Albadri, S., Auer, T.O., Duroure, K., Charpentier, M., Concordet, J.P., Gebhardt, C., Del Bene, F.
Date: 2018
Source: Neuron   97(5): 1049-1062.e6 (Journal)
Registered Authors: Albadri, Shahad, Auer, Thomas, Del Bene, Filippo, De Santis, Flavia, Di-Donato, Vincenzo, Duroure, Karine, Gebhardt, Christoph
Keywords: Reelin, axon guidance, concentration gradient, optic tectum, synaptic laminae, zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Adhesion Molecules, Neuronal/analysis
  • Cell Adhesion Molecules, Neuronal/biosynthesis*
  • Extracellular Matrix Proteins/analysis
  • Extracellular Matrix Proteins/biosynthesis*
  • Nerve Net/chemistry
  • Nerve Net/metabolism*
  • Nerve Tissue Proteins/analysis
  • Nerve Tissue Proteins/biosynthesis*
  • Retinal Ganglion Cells/chemistry
  • Retinal Ganglion Cells/metabolism*
  • Serine Endopeptidases/analysis
  • Serine Endopeptidases/biosynthesis*
  • Synapses/chemistry
  • Synapses/metabolism*
  • Visual Pathways/chemistry
  • Visual Pathways/metabolism*
  • Zebrafish
PubMed: 29429939 Full text @ Neuron
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.