Retinal Ganglion Cell-derived Semaphorin 6A Segregates Starburst Amacrine Cell Dendritic Scaffolds to Organize the Mouse Inner Retina

Overview

Journal Development

Specialty Biology

Date 2024 Nov 4

PMID 39495936

Authors

Rebecca E James

Natalie R Hamilton

Lola Nicole Huffman

Matthew P Brown

Victoria N Neckles

R Jeroen Pasterkamp

Loyal A Goff

Alex L Kolodkin

Affiliations

Soon will be listed here.

Abstract

To form functional circuits, neurons must settle in their appropriate cellular locations, and then project and elaborate neurites to contact their target synaptic neuropils. Laminar organization within the vertebrate retinal inner plexiform layer (IPL) facilitates pre- and postsynaptic neurite targeting, yet the precise mechanisms underlying establishment of functional IPL subdomains are not well understood. Here, we explore mechanisms defining the compartmentalization of OFF and ON neurites generally, and OFF and ON direction-selective neurites specifically, within the developing mouse IPL. We show that semaphorin 6A (Sema6A), a repulsive axon guidance cue, is required for delineation of OFF versus ON circuits within the IPL: in the Sema6a null IPL, the boundary between OFF and ON domains is blurred. Furthermore, Sema6A expressed by retinal ganglion cells (RGCs) directs laminar segregation of OFF and ON starburst amacrine cell dendritic scaffolds, which themselves serve as a substrate upon which other retinal neurites elaborate. These results demonstrate that RGCs, the first type of neuron born within the retina, play an active role in functional specialization of the IPL.

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