Disruption of Neuronal Migration and Radial Glia in the Developing Cerebral Cortex Following Ablation of Cajal-Retzius Cells

Abstract

Cortical neurons are generated within the proliferative layer and follow a strict 'inside-out' gradient of migration and positioning, which determines the characteristic layering and pattern of neural connections in the adult cerebral cortex. Thus, directional migration of postmitotic neuroblasts towards layer I and regulation of the radial glia phenotype subserving cortical migration are central issues in corticogenesis. Recent studies showing that the gene disrupted in the reeler mutation--reelin--is expressed in Cajal-Retzius cells have indicated a role for these pioneer neurons in cortical migration. We show here that ablation of Cajal-Retzius cells in layer I by local application of domoic acid in newborn mice arrests migration of the late-generated neurons, destined to cortical layers II-III, that have been labeled by 5-bromodeoxyuridine injections administered at E16. In addition, degeneration of Cajal-Retzius cells in newborn mice dramatically decreases the number of radial glial apical processes identified by nestin-immunostaining, but increases the number of maturing glial fibrillary acidic protein-positive astrocytes. These findings support an essential role for Cajal-Retzius cells in neuronal migration and corticogenesis, by regulating the identity and function of radial glia and the radial glia-to-astrocyte transformation.

Reelin, Disabled 1, and β 1 integrins are required for the formation of the radial glial scaffold in the hippocampus

“…Reelin molecules, synthesized and secreted by CR cells in the marginal zone (4,5,24), assemble to form a large protein complex (44), suggesting that Reelin acts locally rather than as a freely diffusible factor. Along this line, a dramatic decrease in the number of radial glial apical processes was observed after ablation of CR cells with domoic acid (45). CR cells have been reported to regulate the radial glial phenotype in the cerebellum (46), and an intrinsic glial cell defect has been proposed to contribute to the radial glial malformations in the reeler mutant (47).…”

Multiple roles of chemokine CXCL12 in the central nervous system: A migration from immunology to neurobiology

“…Cortical Cajal-Retzius (CR) cells-In the developing brain cortex, Cajal-Retzius (CR) cells are a transient population of neurons located in the marginal zone (MZ), directly adjacent to the meninges (Derer P and Derer M, 1990;Marin-Padilla M, 1990;Del Rio JA et al, 1995;Verney C and Derer P, 1995). The major function of CR cells is to regulate cortical lamination by secreting the glycoprotein reelin, which maintains the radial glial scaffold that governs the migration of granule cells (D'Arcangelo G et al, 1995;Ogawa M et al, 1995;Super H et al, 2000). Recent studies suggest three major CR cell sources in the embryonic telencephalon, including the cortical hem, the septum and the ventral pallium (TakiguchiHayashi K et al, 2004;Bielle F et al, 2005;Yoshida M et al, 2006).…”

Impaired Neuronal Positioning and Dendritogenesis in the Neocortex after Cell-Autonomous Dab1 Suppression

“…For example, ablation of the Reelinproducing cells (Cajal-Retzius cells) by domoic acid causes premature migration arrest of cells fated for layers 2/3 (Super et al, 2000), and ectopic expression of Reelin in proliferative areas of the developing brain is sufficient to rescue cerebellar development and early, but not later, aspects of neocortical development in reeler mice (Magdaleno et al, 2002). These findings are further complicated by the observations that Reelin signaling can directly stimulate radial glial cell growth and maturation (Hartfuss et al, 2003;Luque et al, 2003).…”