NRP1-mediated Sema3A signals coordinate laminar formation in the developing chick optic tectum

Abstract

The optic tectum comprises multiple layers, which are formed by radial and tangential migration during development. Here, we report that Neuropilin 1 (NRP1)-mediated Sema3A signals are involved in the process of tectal laminar formation, which is elaborated by tangential migration. In the developing chick tectum, NRP1, a receptor for Sema3A, is expressed in microtubule-associated protein 2 (MAP2)-positive intermediate layers IV and V. Sema3A itself is a diffusible guidance factor and is expressed in the overlying layer VI. Using stable fluorescent labeling of tectal cells, we show that MAP2-positive intermediate layers are formed by the neurons that have been dispersed by tangential migration along the tectal efferent axons. When Sema3A was mis-expressed during laminar formation, local Sema3A repelled the tangential migrants, thus eliminating MAP2-positive neurons that expressed NRP1. Furthermore, in the absence of the MAP2-positive neurons, tectal layers were disorganized into an undulated form, indicating that MAP2-positive intermediate layers are required for proper laminar formation. These results suggest that NRP1-mediated Sema3A signals provide repulsive signals for MAP2-positive neurons to segregate tectal layers, which is important in order to coordinate laminar organization of the optic tectum.

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1

“…NRP1 contains a large N-terminal extracellular domain, a short membrane-spanning domain, and a small cytoplasmic domain 26. NRP1 can bind many ligands and various types of coreceptors, such as vascular endothelial growth factor and semaphorin family members 27,28. Through the mediation of several different signaling pathways, NRP1 is involved in the regulation of cell survival and motility 29,30.…”

Engrailed and tectum development

“…; Yamagata & Sanes ; Watanabe et al . ). These molecules may play important roles for formation of the laminar structures in the tectum.…”

Tangential cell migration during layer formation of chick optic tectum

“…We have previously visualized the movement of tangential migration by time‐lapse recording of fluorescent‐labeled cells in a tectal tissue culture (Watanabe et al . ). Tangentially migrating cells hold their bipolar shape with a single motile leading process and a thin trailing process (Fig.…”

“…A), and move in an axophilic‐way clinging to the fasciculus of tectal efferent axons (Movie 1, Movie 2; Watanabe et al . ). Their nuclei have an oblong shape along the proceeding direction, exhibiting salutatory movement with intermittent short periods of slow movement.…”

“…After cutting the tectal axons on which the migrating cells proceeded, the cells stopped at the distal tip of the cut axons then turned back in the opposite direction or restarted, proceeding in the same direction as the following axons elongated (Movie 3, Watanabe et al . ). These features of cell behavior suggest that tectal tangential migration has a locomotion‐type movement using tectal efferent axons as scaffolds for migration.…”