Ariadne’s Thread in the Developing Cerebral Cortex: Mechanisms Enabling the Guiding Role of the Radial Glia Basal Process during Neuron Migration

Abstract

Radial neuron migration in the developing cerebral cortex is a complex journey, starting in the germinal zones and ending in the cortical plate. In mice, migratory distances can reach several hundreds of microns, or millimeters in humans. Along the migratory path, radially migrating neurons slither through cellularly dense and complex territories before they reach their final destination in the cortical plate. This task is facilitated by radial glia, the neural stem cells of the developing cortex. Indeed, radial glia have a unique bipolar morphology, enabling them to serve as guides for neuronal migration. The key guiding structure of radial glia is the basal process, which traverses the entire thickness of the developing cortex. Neurons recognize the basal process as their guide and maintain physical interactions with this structure until the end of migration. Thus, the radial glia basal process plays a key role during radial migration. In this review, we highlight the pathways enabling neuron-basal process interactions during migration, as well as the known mechanisms regulating the morphology of the radial glia basal process. Throughout, we describe how dysregulation of these interactions and of basal process morphology can have profound effects on cortical development, and therefore lead to neurodevelopmental diseases.

Prdm16 and Vcam1 regulate the postnatal disappearance of embryonic radial glia and the ending of cortical neurogenesis

“…Many of these radial glia, and especially those in the cortical walls have endfeet at the pial surface [13][14][15][16][17] . In the cortex, radial processes guide the migration of new neurons generated in the V-SVZ to their final destination in the cortical plate 7,10,14,[16][17][18][19][20][21][22][23] .…”

Novel missense variants in brain morphogenic genes associated with depression and schizophrenia

“…Contemporary research indicates that genetic predisposition plays a pivotal role in the pathogenesis of mental and cognitive disorders ( 2 ). This predisposition can be established during intrauterine development ( 3 , 4 ). Several studies have highlighted that altered gene expression or mutations in proteins encoded by specific genes can disrupt brain development and maturation, leading to brain damage and functional imbalances in the brain’s activating and inhibitory systems.…”

“…Understanding the mechanisms underlying susceptibility to mental diseases and developing approaches for timely diagnosis, prevention, and treatment are essential. Genetic factors are increasingly recognized as contributors to the predisposition for most mental disorders ( 2 ), and impaired brain morphogenesis is believed to be a significant underlying cause ( 3 , 4 ).…”

GPR37L1 controls maturation and organization of cortical astrocytes during development

“…GO ontological analyses on RNA‐seq data from L1KO astrocytes revealed alterations in pathways involved in central nervous system development and brain development. The inclusion of pathways involved in CNS development is particularly intriguing since astrocytes are known to be heavily involved in processes such as guiding neurons to the correct place in the developing brain (Malatesta et al, 2008; Meyerink et al, 2020; Turrero Garcia & Harwell, 2017; Xu et al, 2015) and pruning neuronal synapses (Chung et al, 2013, 2015; Lee & Chung, 2019). Our RNA‐seq analyses further suggest that GPR37L1 regulates expression of astrocytic maturation genes.…”