Embryonic mouse medial neocortex as a model system for studying the radial glial scaffold in fetal human neocortex

Abstract

Neocortex is the evolutionarily newest region in the brain, and is a structure with diversified size and morphology among mammalian species. Humans have the biggest neocortex compared to the body size, and their neocortex has many foldings, that is, gyri and sulci. Despite the recent methodological advances in in vitro models such as cerebral organoids, mice have been continuously used as a model system for studying human neocortical development because of the accessibility and practicality of in vivo gene manipulation. The commonly studied neocortical region, the lateral neocortex, generally recapitulates the developmental process of the human neocortex, however, there are several important factors missing in the lateral neocortex. First, basal (outer) radial glia (bRG), which are the main cell type providing the radial scaffold to the migrating neurons in the fetal human neocortex, are very few in the mouse lateral neocortex, thus the radial glial scaffold is different from the fetal human neocortex. Second, as a consequence of the difference in the radial glial scaffold, migrating neurons might exhibit different migratory behavior and thus distribution. To overcome those problems, we propose the mouse medial neocortex, where we have earlier revealed an abundance of bRG similar to the fetal human neocortex, as an alternative model system. We found that similar to the fetal human neocortex, the radial glial scaffold, neuronal migration and neuronal distribution are tangentially scattered in the mouse medial neocortex. Taken together, the embryonic mouse medial neocortex could be a suitable and accessible in vivo model system to study human neocortical development and its pathogenesis.

Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development

“…Furthermore, while GLT-1 is mainly expressed in neurons transiently during the neurogenic period in several mammalian species 36 – 38 , GLAST (glutamate aspartate transporter) is a known classical marker protein of radial glia in both embryonic mouse neocortex (Supplementary Fig. 6a, b ) 39 , 40 and fetal human neocortex 32 , 41 . We therefore explored a possible requirement of GLAST for the increased bRG abundance observed in the neocortex of embryos of the ARHGAP11B + GLUD2 mice, by crossing these mice with previously established GLAST knockout (KO) mice 42 .…”

Dynamic changes in mitochondrial localization in human neocortical basal radial glial cells during cell cycle

“…Fetal human brain tissues (gestational week [GW] 18-and 19) were obtained from the Helsinki University Hospital, with approval by the ethics committee of the Hospital District of Helsinki and Uusimaa (HUS/1170/2021). The tissues were processed as previously described (Vaid et al, 2023). Fetal human brain tissues were dissected in PBS and then transferred immediately into 4% paraformaldehyde for fixation overnight at 4 • C. The tissues were washed with PBS, and then 30% sucrose in PBS for immunohistochemistry.…”