Radial Glial Dependent and Independent Dynamics of Interneuronal Migration in the Developing Cerebral Cortex

Abstract

Interneurons originating from the ganglionic eminence migrate tangentially into the developing cerebral wall as they navigate to their distinct positions in the cerebral cortex. Compromised connectivity and differentiation of interneurons are thought to be an underlying cause in the emergence of neurodevelopmental disorders such as schizophrenia. Previously, it was suggested that tangential migration of interneurons occurs in a radial glia independent manner. Here, using simultaneous imaging of genetically defined populations of interneurons and radial glia, we demonstrate that dynamic interactions with radial glia can potentially influence the trajectory of interneuronal migration and thus the positioning of interneurons in cerebral cortex. Furthermore, there is extensive local interneuronal migration in tangential direction opposite to that of pallial orientation (i.e., in a medial to lateral direction from cortex to ganglionic eminence) all across the cerebral wall. This counter migration of interneurons may be essential to locally position interneurons once they invade the developing cerebral wall from the ganglionic eminence. Together, these observations suggest that interactions with radial glial scaffold and localized migration within the expanding cerebral wall may play essential roles in the guidance and placement of interneurons in the developing cerebral cortex.

Regional Distribution of Cortical Interneurons and Development of Inhibitory Tone Are Regulated by Cxcl12/Cxcr4 Signaling

“…1 B, yellow arrowheads (available at www.jneurosci.org as supplemental material)]. This is consistent with previous studies demonstrating that the superficial and deep interneuron streams have some exchange as well as the tendency of many interneurons to migrate in a variety of directions within local zones (Ang et al, 2003;Tanaka et al, 2003;Yokota et al, 2007 Fig. 1 E (available at www.jneurosci.org as supplemental material)].…”

“…1 B-E, white arrowheads (available at www.jneurosci.org as supplemental material)]. These dynamic changes in the distributions of Lhx6-GFPϩ cells are consistent with the observations of others using different labeling approaches (Ang et al, 2003;Tanaka et al, 2003;Yokota et al, 2007) and provide an anatomical and temporal framework for assessing the mechanisms that regulate the tangential and radial migration of these immature interneurons.…”

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

“…Prominent SPARC expression also persists in cortical radial glial at P5 (Fig. 3), and may be involved in the axial migration of late-born projection neurons and interneurons, which utilize glial-guided migration in the embryo (Rakic, 1972;Yokota et al, 2007), during the first postnatal week (Hevner et al, 2004). In the adult brain, specialized radial glia-like cells that are associated with ongoing plasticity and cell migration continue to express SPARC, including Bergmann glia in the cerebellum (Fig.…”

Netrin-1–α3β1 integrin interactions regulate the migration of interneurons through the cortical marginal zone

“…Neuronal progenitors from the dorsal telencephalon migrate radially as cohorts along the radial glial scaffold, pass their predecessors in the developing cortical plate, and coalesce into layers, giving rise to glutamatergic projection neurons (1). In contrast, neuronal precursors from the ventral telencephalon, principally the medial ganglionic eminence (MGE), migrate tangentially through the cortical marginal zone and intermediate zone and enter the cortical plate, using the radial glial scaffold, before differentiating into GABAergic interneurons (2)(3)(4). A subset of these interneurons initially migrates radially inwards, toward the cortical ventricular zone, before turning back up toward the cortical plate (4).…”

“…In contrast, neuronal precursors from the ventral telencephalon, principally the medial ganglionic eminence (MGE), migrate tangentially through the cortical marginal zone and intermediate zone and enter the cortical plate, using the radial glial scaffold, before differentiating into GABAergic interneurons (2)(3)(4). A subset of these interneurons initially migrates radially inwards, toward the cortical ventricular zone, before turning back up toward the cortical plate (4). These different modes of neuronal migration are coordinated temporally to achieve the ''inside-out'' laminar organization of neurons in the neocortex.…”