Migration Speed of Cajal-Retzius Cells Modulated by Vesicular Trafficking Controls the Size of Higher-Order Cortical Areas

Abstract

In the neocortex, higher-order areas are essential to integrate sensory-motor information and have expanded in size during evolution. How higher-order areas are specified, however, remains largely unknown. Here, we show that the migration and distribution of early-born neurons, the Cajal-Retzius cells (CRs), controls the size of higher-order areas in the mouse somatosensory, auditory, and visual cortex. Using live imaging, genetics, and in silico modeling, we show that subtype-specific differences in the onset, speed, and directionality of CR migration determine their differential invasion of the developing cortical surface. CR migration speed is cell autonomously modulated by vesicle-associated membrane protein 3 (VAMP3), a classically non-neuronal mediator of endosomal recycling. Increasing CR migration speed alters their distribution in the developing cerebral cortex and leads to an expansion of postnatal higher-order areas and congruent rewiring of thalamo-cortical input. Our findings thus identify novel roles for neuronal migration and VAMP3-dependent vesicular trafficking in cortical wiring.

Tangential migration of glutamatergic neurons and cortical patterning during development: Lessons from Cajal‐Retzius cells

“…Thus, CR subtypes appear to act as “mobile patterning units” and signal to pallial progenitors to influence the spatial patterning and regionalization of the cortex and the formation of postnatal cortical areas (Griveau et al, ). Consistent with this, a recent study has shown that by genetically modulating the migration velocity of CR subtypes, this altered CRs specific distributions and compositions at the cortical surface which, in turn, resulted in changes in the size of secondary and association areas of the somatosensory, auditory and visual cortex at postnatal stages and in a congruent rewiring of thalamocortical afferents in primary somatosensory areas (Barber et al, ). These studies raise the intriguing possibility that changes in the total number of CRs influence primary cortical area formation (Griveau et al, ), with changes in the specific composition of CR subtypes influencing the size of higher‐order cortical areas (Barber et al, ).…”

“…Consistent with this, a recent study has shown that by genetically modulating the migration velocity of CR subtypes, this altered CRs specific distributions and compositions at the cortical surface which, in turn, resulted in changes in the size of secondary and association areas of the somatosensory, auditory and visual cortex at postnatal stages and in a congruent rewiring of thalamocortical afferents in primary somatosensory areas (Barber et al, ). These studies raise the intriguing possibility that changes in the total number of CRs influence primary cortical area formation (Griveau et al, ), with changes in the specific composition of CR subtypes influencing the size of higher‐order cortical areas (Barber et al, ). Indeed, during postnatal stages, CRs integrate into and shape cortical circuitry (Zhou and Hablitz, ; Zhou and Hablitz, ; Aguilo et al, ; Radnikow et al, ; Albrieux et al, ; Quattrocolo and Maccaferri, ).…”

Cajal-Retzius cells: organizers of cortical development

“…These effects were most probably caused by a direct effect of this CRc subpopulation on neuroblasts in the ventricular zone via secreted molecules, putatively fibroblast growth factors [30]. In line with this, the redistribution of different CRc subpopulations after selective alteration of migratory rates in Vamp3-inactivated CRc shifts the localization of primary and secondary sensory areas in the mouse neocortex [6], further emphasizing that CRc can impose regionalization cues to the immature neocortical anlage.…”

“…Interestingly, the interaction between CXCL12 and CXCR4 induces a strong hyperpolarization and reduces the excitability of CRc [53], suggesting that chemical cues and electrical signals can interact during structural development. The migration rate of CRc is enhanced after cell-type selective inactivation of Vamp3, which is required for exocytosis of soluble factors, indicating that autocrine processes may be involved in the regulation of CRc migration [6].…”

Quand la migration de neurones signalisateurs contrôle la régionalisation du cortex cérébral

“…Une étude récente menée au sein de notre laboratoire [11] indique que les différentes sous-populations de cellules de CajalRetzius n'ont pas les mêmes cinétiques de migration, ce qui détermine leur réparti-tion spécifique à la surface du cortex en développement. Des approches de vidéo-microscopie et des simulations mathéma-tiques nous ont permis de déterminer que la vitesse et la directionalité sont des paramètres essentiels pour la distribution finale de chaque sous-population.…”