Localized astrogenesis regulates gyrification of the cerebral cortex

Abstract

The development and evolution of mammalian higher cognition are represented by gyrification of the laminar cerebral cortex and astrocyte development, but their mechanisms and interrelationships remain unknown. Here, we show that localized astrogenesis plays an important role in gyri formation in the gyrencephalic cerebral cortex. In functional genetic experiments, we show that reducing astrocyte number prevents gyri formation in the ferret cortex, while increasing astrocyte number in mice, which do not have cortical folds, can induce gyrus-like protrusions. Morphometric analyses demonstrate that the vertical expansion of deep pallial regions achieved by localized astrogenesis is crucial for gyri formation. Furthermore, our findings suggest that localized astrogenesis by a positive feedback loop of FGF signaling is an important mechanism underlying cortical folding in gyrencephalic mammalian brains. Our findings reveal both the cellular mechanisms and the mechanical principle of gyrification in the mammalian brain.

Erratic and blood vessel-guided migration of astrocyte progenitors in the cerebral cortex

“…Neurons were labeled with an α-tubulin (Tα1) promoter-driven GFP expressing vector (Tα1-EGFP). To label astrocyte progenitors, we used a Cre-dependent red fluorescent protein (RFP)-expressing PiggyBac transposon vector (pPB-CAG-LNL-turboRFP) 15 , 16 , which is integrated into the host genome with the help of a transposase-expressing vector (pCAG-hyPBase), and can efficiently label proliferative astrocyte lineage cells 9 , 17 , 18 . Cre was expressed under the human GFAP promoter (hGFAP-Cre), which is preferentially active in the astrocyte lineage.…”

Cortical morphological heterogeneity of schizophrenia and its relationship with glutamatergic receptor variations

“…GRM3 gene was involved in the synthesis of metabolic glutamate receptor subunit 3, which can inhibit cyclic adenosine monophosphate [90] and reduce Ca 2+ flow through NMDA receptor, and achieve antioxidant and antineurotoxic effects. Interestingly, animal studies indicate that aberrant gyrification may arise from deficits in astroglial support [91], which may also relate to glutamatemediated toxicity during development [92]. Note that the effect of these genetic variations may differ across brain regions (see Supplementary Figure S1).…”

Investigation of the mechanisms underlying the development and evolution of folds of the cerebrum using gyrencephalic ferrets

“…Consistently, it has been recognized that as cortical folds developed and the cerebrum expanded during evolution, there was a significant increase in the number of glial cells (Herculano‐Houzel, 2014). To examine the molecular mechanisms regulating the evolutionary increase in astrocytes, we compared astrocyte gene expression between mice and ferrets (Shinmyo et al., 2022). Ferret astrocytes exhibited elevated FGF1 expression compared to their mouse counterparts.…”