A Role of Netrin-1 in the Formation of the Subcortical Structure Striatum: Repulsive Action on the Migration of Late-Born Striatal Neurons

Abstract

The mammalian striatum arises in the basal telencephalon and contains morphologically homogenous neurons that can be divided into two distinct compartments, patches and the matrix. During development, patch neurons are generated first to form a striatal primordium. After a large influx of later-born matrix neurons into this region, the unique mosaic arrangement of these two neuronal phenotypes is established. The massive migration of matrix neurons continues during the embryonic period, and they eventually comprise 80-85% of the mature striatum. To elucidate the cellular mechanism or mechanisms underlying this critical event in striatal histogenesis, we examined the migration characteristics of striatal subventricular zone (SVZ) cells at embryonic day 18 when neurogenesis peaks for matrix neurons. Using gel cultures, we show that netrin-1, one of the diffusible guidance cues expressed in the striatal ventricular zone (VZ), exerts a repulsive action on migrating SVZ cells. This effect is blocked in the presence of antibodies against Deleted in colorectal cancer (DCC), a putative receptor for netrin-1. The expression patterns of netrin-1 and DCC strongly suggest the involvement of this effect in the outward migration of SVZ cells into the striatal postmitotic region. Our cell tracing study using living brain slices demonstrates that striatal SVZ cells migrate toward and disperse throughout the striatum, in which they differentiate into phenotypes of striatal projection neurons. We suggest that netrin-1 expressed in the striatal VZ serves to guide the large influx of striatal matrix neurons into the striatal primordium and is thereby involved in the initial formation of fundamental striatal structures.

Molecular Control of Spinal Accessory Motor Neuron/Axon Development in the Mouse Spinal Cord

“…Consistent with the ability of the floor plate (Colamarino and Tessier-Lavigne, 1995b;Guthrie and Pini, 1995;Tucker et al, 1996) and netrin-1 (Varela-Echavarria et al, 1997; Alcantara et al, 2000;Hamasaki et al, 2001) to repel hindbrain or spinal motor axons/cell bodies, a subset of SACMN cell bodies/ axons fails to migrate dorsally in both netrin-1 and Dcc mutants. The observation that BEN-positive SACMNs are likely to express Dcc mRNA supports a cell-autonomous role for DCC in mediating the presumed repulsion of SACMNs and their axons.…”

Shear flow-induced motility ofDictyostelium discoideumcells on solid substrate

“…in SFICM, actin polymerization occurs on the side opposite to the zone of maximum stress. This is more comparable to repulsive chemotaxis, as seen (for instance) in the response of axon growth cones to diffusible chemorepellents such as netrins (Hamasaki et al, 2001;Tessier-Lavigne and Goodman, 1996).…”

Origin and Molecular Specification of Globus Pallidus Neurons

“…In the basal telencephalon, at least two nuclear structures seem to develop following the same principles. In the striatum, projection neurons appear to migrate radially from the LGE (Halliday and Cepko, 1992;Hamasaki et al, 2001), whereas interneurons reach their target from the MGE by tangential migration (Marín et al, 2000). Similarly, recent work has shown that the medial nucleus of the amygdala also forms by gathering radially migrating projection neurons from the LGE and tangentially migrating interneurons from the POA (Carney et al, 2006;Hirata et al, 2009).…”