Radial glia regulate Cajal–Retzius cell positioning in the early embryonic cerebral cortex

Abstract

The organization of neocortex, along its radial axis, into a six-layered structure is one of the most exquisite features of the brain. Because of their strategic localization in the marginal zone, and their expression of reelin, a signal that controls spatial ordering of cortical layers, Cajal-Retzius (C-R) cells play a crucial role in cortical patterning along this axis. Yet, it remains less well understood how C-R cell targeting itself is regulated. At the onset of corticogenesis when C-R cells first arrive in the cortex via tangential migration, radial glia (RG) are the main cell type present. This suggests that RG may play a role in C-R cell localization. To test this, we used genetic approaches to perturb RG scaffold during early corticogenesis. We found that disrupting RG endfoot adhesion to basal lamina consistently results in C-R cell displacement. These displacements do not appear to result from primary defects in neural progenitor cell proliferation, deficits in the meninges or basement membrane, or cell autonomous defects in C-R cells. Instead, they show close temporal and spatial correlation with RG endfoot retraction. Moreover, ablation of RG via cell cycle blockade similarly results in local displacement of C-R cells. These lines of evidence thus indicate that, during early corticogenesis, RG play a primary role in regulating spatial targeting of C-R cells. Since RG are also neural progenitors as well as neuronal migration scaffolds, these findings suggest that, during nervous system development, neuroepithelial stem cells may not only be responsible for generating a diverse array of neuronal cell types and facilitating their radial migration. They may also, through regulating the placement of guidepost cells, coordinate spatial patterning of the nervous system along its radial axis.

A Functional Requirement for Astroglia in Promoting Blood Vessel Development in the Early Postnatal Brain

“…Peroxidase conjugated secondary antibodies were purchased from Santa Cruz Biotech. Staining procedures were performed as described previously [32], and sections were mounted with Fluoromount G medium (Southern Biotech, Birmingham, AB) and analyzed under a Nikon eclipse Ti microscope or an Olympus confocal microscope. For 3-D reconstruction, NIH ImageJ software was employed.…”

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

“…A recent study reported that the distribution of CR cells is also mediated by radial glial cells 67 . Indeed, an absence of radial glia results in local displacement of CR cells in layer I 67 .…”

“…Indeed, an absence of radial glia results in local displacement of CR cells in layer I 67 . In addition, the expression of Sema3E by radial glia at the subpallium in the lateral ganglionic eminence has been recently suggested 31 .…”

Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration

“…For example, Cdk5 is required cellautonomously in both (Hirasawa et al, 2004;Ohshima et al, 2007), Dab1 is required only in migrating neurons (Franco et al, 2011), whereas β1 integrins (Belvindrah et al, 2007) and RhoA (Cappello et al, 2012) are radial glia specific. Ccm3 (this study) and Itgb1 mutants display neuronal migration and cortical lamination defects (Graus-Porta et al, 2001;Schmid et al, 2004;Huang et al, 2006;Marchetti et al, 2010), pial detachment of endfeet (Graus-Porta et al, 2001;Kwon et al, 2011) and reactive gliosis (Robel et al, 2009), suggesting a -possibly indirectinteraction that warrants investigation, especially given the association of CCM1 with ICAP1α, which binds the β1 integrin cytoplasmic tail (Zawistowski et al, 2002;Faurobert et al, 2013). On the other hand, RhoA is necessary in radial glia to stabilize the actin and microtubule cytoskeletons, and to maintain the radial glia scaffold (Cappello et al, 2012); thus, our findings that RhoA is activated in Ccm3 conditional mutants could partially explain the migration defects.…”