Del Bene - neural circuit development / CRISPR

Speaker: Filippo Del Bene, Group Leader at Institut Curie, Paris

Title: Deciphering anatomy and development of neural circuits in the zebrafish in the CRISPR/Cas9 era

Date: Wednesday, July 19, 2017 17:00 pm

Location: CCO auditorium


The specificity of connections between neurons ensures proper neural circuit function and thus constitutes the basis for perception and behavior initiation. Axon-dendrite connections are often anatomically segregated into synaptic laminae, frequently devoted to specific sensory information processing. Although synaptic lamination represents a conserved organizational and functional principle of neural networks, at present a comprehensive model for their establishment remains lacking. Here we show that the secreted protein Reelin is critical for the cytochemical pre-patterning of synaptic laminae in the vertebrate visual system. In particular, we unveil a previously unidentified role of Reelin as a wiring molecule that coordinates targeting of growing retinal afferents via the receptor VLDLR and the intracellular transducer Dab1a. Furthermore, we find that Reelin is distributed in a concentration gradient within the target tissue and that this gradient is stabilized by heparan sulfate proteoglycans (HSPGs) in the extracellular matrix (ECM). Finally, we demonstrate that target-derived Reelin exerts an attractive effect on RGC axons, enabling them to identify their specific target lamina. Almost 30 years ago, theoretical studies established that axons are steered to their correct target zone by at least two counteracting molecular forces per target axis such that axons stop along the axis where the two forces are exactly balanced. Although a recent study proposed that retinal axon lamination is influenced by repulsive Slit1 signaling, this molecular force alone cannot account for the steering of ingrowing axons toward their proper target laminae. By identifying attractive Reelin signaling as a force that counter-balances the repulsive activity of Slit1, our study provides the first experimental evidence for a comprehensive model of lamina formation in which these signals direct RGC axons toward their synaptic lamina. Notably, this mechanism may represent a general principle for neural network assembly in other species and brain areas.

Related literature:

Dunn et al, (2016) Neural Circuits Underlying Visually Evoked Escapes in Larval Zebrafish, Neuron : 89 : 3 : 613-628
Auer et al (2014) CRISPR/Cas9-mediated conversion of eGFP- into Gal4-transgenic lines in zebrafish. Nature Protocols : 2823-40
Auer et al (2014) Deletion of a kinesin I motor unmasks a mechanism of homeostatic branching control by neurotrophin-3. eLife : DOI : 10.7554/eLife.05061
Del Bene et al (2010) Filtering of visual information in the tectum by an identified neural circuit. Science : 669-73


HOST: Benjamin Judkewitz (feel free to get in touch if you’d like to meet with the speaker)

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