Lecture 1: Dysfunction of Neural Stem Cells in the Developing and Adult Brain – Dr Daniel Berg Flashcards
How does the cortex develop?
Cortex development involves neurogenesis, starting with neural stem cells, and includes processes like radial glial cell formation, cell migration, and layer formation.
Name different cell types in brain generation
Neural stem cells give rise to radial glia, intermediate progenitor cells, neurons, astrocytes, and oligodendrocyte progenitor cells during brain development.
Neurogenesis issues and study methods
Neurogenesis issues may lead to disorders. Studied through techniques such as RNA sequencing, organoids, and analysis of cell types and communication at various levels
Microcephaly, macrocephaly, lissencephaly
Microcephaly: small head, intellectual disability. Macrocephaly: large head, mTOR pathway disruption. Lissencephaly: smooth brain surface, often due to genetic deletion (Miller-Dieker syndrome).
Communication between brain regions
Networks involve interactions at the level of synapses, cells, populations, and entire brain regions.
Cortex structure analysis levels
Study the brain at network, population, cell, synapse, and nucleus levels to understand its complexity.
Neuronal comparison with elephants
Humans have three times as many neurons in the cortex as elephants; this reflects cognitive and computational capabilities.
Functions of cerebral cortex lobes
Each lobe has distinct functions. Frontal: motor control, reasoning. Parietal: sensory information. Temporal: auditory and visual processing. Occipital: visual processing.
RNA sequencing in cortex lobes
Despite cortical lobe divisions, RNA sequencing reveals a diverse range of cell types, indicating a complex system.
Neural stem cells origin
All brain cells originate from neural stem cells, initially called neuroepithelial cells.
Cortex development timeline
Most neurogenesis in the cortex occurs before birth. Folding occurs at 8-9 months, followed by myelin development after birth.
Radial glia in cortex development
Neuroepithelial cells transform into radial glia, producing neural intermediate progenitor cells and various cell types.
Types and functions of glial cells
Astrocytes and oligodendrocytes provide structural and functional support, contributing to synapse formation and myelination.
Neuronal migration along radial fibers
Radial fibers serve as scaffolding for migrating neurons. In mice, these columns relate to the patterning of whiskers.
Ventricular zone in brain development
The ventricular zone contains ventricular radial glia, serving as the origin of neural cells during cortical development.
Outer radial glia in humans
Outer radial glia cells appear later, contributing to cortical development, expressing similar markers as ventricular radial glia.
Mechanism of outer radial glia generation
Neuroepithelial cells self-renew, ventricular radial glia divide vertically, and outer radial glia divide horizontally.
Notch signaling in development
Notch signaling is involved in cell fate determination during cortical development.
Layers of developing cortex
Layers include ventricular zone, inner and outer subventricular zones, intermediate zone, cortical plate, marginal zone, and pial surface.
Hippocampus neurogenesis
The hippocampus is unique, with neurogenesis occurring from birth into adulthood, involving radial glial-like cells.
Organoids and brain development
Brain organoids derived from reprogrammed fibroblasts mimic specific brain areas and provide a 3D culture for studying brain development.
Seckel syndrome and CPAP gene
Seckel syndrome, caused by a CPAP gene mutation, leads to intellectual disability, microcephaly, and altered cortical development.
Zika virus and microcephaly
Zika virus primarily infects neural stem cells, causing microcephaly by reducing neural stem cell proliferation and thickness of the ventricular zone.
Measuring brain disorders ethically
Organoids offer an ethical alternative to animal models, revealing insights into disorders like Meckelencephaly (macro) and Lissencephaly.
