Toward an understanding of glucose metabolism in radial glial biology and brain development

Abstract

Decades of research have sought to determine the intrinsic and extrinsic mechanisms underpinning the regulation of neural progenitor maintenance and differentiation. A series of precise temporal transitions within progenitor cell populations generates all the appropriate neural cell types while maintaining a pool of self-renewing progenitors throughout embryogenesis. Recent technological advances have enabled us to gain new insights at the single-cell level, revealing an interplay between metabolic state and developmental progression that impacts the timing of proliferation and neurogenesis. This can have long-term consequences for the developing brain’s neuronal specification, maturation state, and organization. Furthermore, these studies have highlighted the need to reassess the instructive role of glucose metabolism in determining progenitor cell division, differentiation, and fate. This review focuses on glucose metabolism (glycolysis) in cortical progenitor cells and the emerging focus on glycolysis during neurogenic transitions. Furthermore, we discuss how the field can learn from other biological systems to improve our understanding of the spatial and temporal changes in glycolysis in progenitors and evaluate functional neurological outcomes.

High-resolution 3D ultrastructural analysis of developing mouse neocortex reveals long slender processes of endothelial cells that enter neural cells

“…In contrast, in the avascular VZ, APs are maintained in their proliferative state by the interaction with ETCs ( Komabayashi-Suzuki et al, 2019 ; Di Marco et al, 2020 ). The specificity of these different niches is reflected by different modes of metabolism, induced by bi-directional signaling between HIF-1α- and VEGF-expressing APs and endothelial cells sprouting into the avascular niche of the VZ ( Namba et al, 2021 ; Dong et al, 2022 ; Andrews and Pearson, 2024 ). One way these effects on metabolism may be induced, irrespective of oxygenation by already formed blood vessels, is that ETCs might regulate the metabolic state of neural cells by releasing factors like the HIF-1α—downstream factor apelin, which modulates endothelial cell metabolism ( Helker et al, 2020 ).…”