An Attractive Reelin Gradient Establishes Synaptic Lamination in the Vertebrate Visual System

They establish a mechanism that may represent a general principle for neural network assembly in vertebrate species and across different brain areas.

Vincenzo Di Donato 1Flavia De Santis 1Shahad Albadri 1Thomas Oliver Auer 1Karine Duroure 1Marine Charpentier 2Jean-Paul Concordet 2Christoph Gebhardt 3Filippo Del Bene 4

ABSTRACT

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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