BY OUR PLATFORMS
BY THERAPEUTIC AREA
07 March 2018
Vincenzo Di Donato 1, Flavia De Santis 1, Shahad Albadri 1, Thomas Oliver Auer 1, Karine Duroure 1, Marine Charpentier 2, Jean-Paul Concordet 2, Christoph Gebhardt 1, Filippo Del Bene 1
1Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, UPMC Paris-Sorbonne, Paris 75005, France.
2Muséum National d'Histoire Naturelle, INSERM U1154, CNRS UMR7196, Paris 75231, France.
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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