Student name: Venka De Rooij
Institution: King’s College London
Course: 7PAMFBIO, Biological Foundations of Mental Health
Practice: Grey Matters Therapy
Introduction
Brain cortex development involves cell-type synchronization throughout numerous phases. Radial glial cells significantly influence neurogenesis and migration, which shape the growing brain’s intricate architecture. Radial glial cells can differentiate into neurons and glial cells, enhancing cortical cell variety. Genetic destiny mapping and cell lineage tracing were used. This essay will analyze the numerous signaling channels that influence radial glial activity, focusing on Yokota et al.’s (2010) groundbreaking work on Cdc42 and Gsk3. It also examines neurogenesis and radial glial cell differentiation into intermediate progenitors. This analysis uses multiple sources to show how radial glial cells maintain the delicate balance between neurogenesis and migration, which affects brain creation and evolution.
Cdc42 inhibition inhibited radial glial growth, damaging the scaffold. The scaffold rupture caused cortical neuron misplacement. These findings demonstrate Cdc42’s role in radial glial cells’ scaffold-like activity throughout cortical development. After Gsk3 inhibition, we also saw changes in inter-radial glial connections and altered radial glial polarity (Meyer, 2007). Mouse radial glial polarity disruption caused neuronal migration abnormalities in the developing cortex. The expression of crucial molecules involved in cell adhesion and polarity was altered by Gsk3 inhibition, further highlighting its role in regulating the behavior of radial glial cells.
Radial glial cells as neuronal progenitor cells
For neurogenesis in the cerebral cortex, radial glial cells are required. Traditional research methods, such as tracing cell lineages and determining genetic destinies, can demonstrate their potential for neurogenesis. Radial glial cells support migratory neurons and produce their brain cells. This indicates that radial glial cells have a dual role in brain development. Genetic destiny mapping was first introduced by the groundbreaking work of Hagey et al. (2020) in the growing mouse brain. During the process of corticogenesis, they discovered that radial glial cells can differentiate into either neurons or glial cells because they are multipotent; like stem cells, radial glial cells can differentiate into many different cell types necessary for normal brain development.
The uneven division of radial glial cells has also been studied with time-lapse imaging and genetic lineage tracking. When radial glial cells split, they create a new radial glial cell and a neuron, as shown by Gallo et al. (2020). Neurogenic cell division, which occurs when radial glial cells divide, also develops new neurons. The ability of radial glial cells to produce neurons and glial cells significantly affects how the cortex forms. Stem cells, in their capacity as progenitors throughout the neurogenesis process, have the potential to maintain a high brain-wide neuronal population, allowing for continued cortical development and growth. The progenitor potential of glial cells is crucial for neuronal survival, connection modulation, and homeostasis maintenance, according to research by Guarnieri et al. from 2022.
Self-renewal and neurogenic potential of radial glial cells
Time-lapse imaging and genetic fate mapping experiments support the integrity of these characteristics. Hickmott et al.’s 2021 study found that radial glial cells’ ability to self-renew is greatly enhanced by asymmetric cell division. The neurogenic division is a common mechanism for radial glial cell reproduction. New neurons, intermediate stem cells, and radial glial cells could all develop. This strategy can maintain a stable population of radial glial cells, boosting the generation of new neurons or progenitor cells. Experiments corroborate the findings of Urbán et al. (2019) that the Notch pathway is essential for maintaining the neural stem cell properties of radial glia and suppressing their premature differentiation into neurons. Radial glia retains their neural stem cell properties, according to research published in 2019 by Urbán et al., and the Notch pathway plays a crucial role in this process.
Cortical layering and circuit creation rely on the self-renewal and neurogenesis capabilities of radial glial cells, which allow them to create distinct neuronal subtypes in an ordered fashion. Regeneration medicine and therapies targeting the regeneration potential of neural stem cells to treat neurological illnesses and brain injuries may benefit greatly from a complete understanding of the molecular mechanisms underlying these processes (Huang et al., 2020). More study is needed to decipher the intricate regulatory networks that determine the radial glial cell fate in the embryonic cortex.
Transition of radial glial to intermediate progenitors
The connection between radial glia and intermediate progenitors is essential for cortical development. Both neurogenesis and neuronal diversity are boosted during this phase change. Intermediate progenitor cells develop from the neural stem cell-maintaining radial glial cells. De Gioia et al. (2020) found that developing cortical radial glial cells divide asymmetrically. These cell divisions produce radial glial and post-mitotic neurons or intermediate progenitor cells. Some radial glial cells transform into neurogenic neurons when the embryonic cortex matures and begin dividing symmetrically. Without an apical process, the subventricular zone (SVZ) and outer SVZ (oSVZ) distinguish cells in the developing cortex. In addition, subventricular features can be seen in these areas. The cells can divide quickly and symmetrically, which results in a more significant number of freshly generated neurons. Hagey et al. (2020) claim that neurons for the different cortical layers originate from intermediate progenitor cells that move to the cortical plate and undergo terminal divisions there.
Several signaling pathways and transcription factors control radial glia to intermediate progenitors. Notch signaling downregulation preserves radial glial cells as neural stem cells. They can become neurons. According to Adeyinka & Egger (2022), Tbr2 (Eomes), and NeuroD1, transcription factors enhance the neurogenic destiny and neuronal development of intermediate progenitors. Radial glia can differentiate into intermediate progenitors in the developing nervous system in response to external cues and extracellular signaling. Meningeal sonic hedgehog (Shh) activation induced intermediate progenitor differentiation of radial glial cells in the outer subventricular zone (Penisson et al., 2019).
Radial cells and brain evolution
Comparative studies have linked radial glial cells to larger, more complex brains. Radial glial cells, more abundant and organized in higher-order primates and humans, guide new neuron migration throughout complicated cortical construction (Huang et al., 2020). This is because they are crucial in controlling the motion of extra neurons. The neurogenic potential of radial glial cells profoundly affects brain development and their function in neuronal migration. To generate a wider variety of neuron types and create more complex neural circuits, species with larger brains and more developed cognitive abilities must enhance neurogenesis.
Radial glial cells are perfectly equipped to fill this need because they can self-renew and produce various daughter cells (Ferent et al., 2020). By contrasting the expression of genes associated with this cell type, it has also been possible to identify evolutionary alterations in the regulatory networks that control the activity of radial glial cells. These regulatory networks govern the radial glial cells. Radial glial cells are crucial for brain growth, but their significance in evolution is far higher (Crino et al., 2002). Radial glia-like cells, which have been demonstrated to persist into adulthood, may be involved in neuronal plasticity and repair following learning or damage.
Conclusion
In conclusion, radial glial cells perform a critical and multifaceted role in brain development, serving as both neural progenitors and guides for neuronal migration. Their remarkable capacity for self-renewal and the generation of new neurons ensures a continuous pool of neural stem cells throughout corticogenesis. Through self-renewing asymmetric division, radial glial cells produce both new radial glial cells and neurons, contributing to the proper formation of the cerebral cortex. The generation of diverse neural cell types, including neurons and other glial cells, highlights their multipotent nature and their significance in shaping the complexity of the brain’s cellular composition. Advanced imaging and genetic studies have provided compelling evidence supporting radial glial cells’ role as neuronal progenitors, confirming their dynamic behavior during neurogenesis. Regarding their relative contribution in comparison to other progenitor cell types, such as intermediate progenitors (IPs), there still exists debate. IPs have been found to be important neurogenesis contributors, boosting the neuronal pool during constrained divisions. Further complicating individuals’ knowledge of the role played by radial glial cells is the possibility that the method of neurogenesis differs between various brain regions and developmental stages. However, given their pivotal function in brain development and the possibility that they participate in adult neurogenesis, further research is required to fully understand the intricacies of neural progenitor hierarchies and the mechanisms regulating brain development.
