Lecture 15: Neural Stem cells, MS, and Parkinson’s
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Questions and Answers

What role do morphogen gradients play in brain development?

  • They help pattern the developing tube and guide cell production. (correct)
  • They solely determine the appearance of B cells.
  • They inhibit the production of neurons in the adult brain.
  • They universally produce all types of cells along the ventricular surface.

Which statement about B cells in the adult brain is correct?

  • They remain identical in appearance to radial glial cells throughout life.
  • They are inactive and do not produce new neurons.
  • They exclusively produce glial cells in adulthood.
  • They can produce neurons but differ in appearance and functionality from earlier developmental stages. (correct)

What is a unique aspect of human brain development compared to other species?

  • The brain develops without the influence of signaling gradients.
  • The outer subventricular zone does not expand in humans.
  • Neuronal production ceases upon reaching adulthood in humans.
  • Humans have a significantly expanded outer subventricular zone. (correct)

What does the outer subventricular zone contribute to in human brain development?

<p>It generates a larger cortex and increases cortical cell numbers. (B)</p> Signup and view all the answers

How do different regions along the ventricular surface influence brain cell production?

<p>They produce distinct types of cells, maintaining diversity into adulthood. (D)</p> Signup and view all the answers

Which primary vesicle is associated with the development of the cerebral hemispheres?

<p>Prosencephalon (D)</p> Signup and view all the answers

What structure is derived from the metencephalon?

<p>Cerebellum (D)</p> Signup and view all the answers

Which of the following is a derivative of the mesencephalon?

<p>Midbrain (C)</p> Signup and view all the answers

Which primary vesicle gives rise to the myelencephalon?

<p>Rhombencephalon (D)</p> Signup and view all the answers

What is the primary role of the ventricular system in relation to neural development?

<p>Persistent formation from the neural tube (C)</p> Signup and view all the answers

Which of the following structures is found in the third ventricle?

<p>Hypothalamus (D)</p> Signup and view all the answers

Which brain structure is partially formed from the fourth ventricle?

<p>Pons (D)</p> Signup and view all the answers

What is NOT a function of radial glial cells?

<p>Formation of new oligodendrocytes (A)</p> Signup and view all the answers

What is produced during vertical plane cleavage in radial glial cells?

<p>Two identical daughter cells (D)</p> Signup and view all the answers

Which statement about interkinetic nuclear migration (IKNM) is true?

<p>It involves oscillation of nuclei between the ventricular and pial surfaces (C)</p> Signup and view all the answers

What is a characteristic of outer radial glial cells (oRGCs)?

<p>They divide to produce daughter cells that migrate and contribute to cortical growth (C)</p> Signup and view all the answers

Why do humans have a greater complexity in the cortex compared to mice?

<p>Increased presence of outer radial glial cells (B)</p> Signup and view all the answers

Which type of cleavage occurs later in the development of radial glial cells?

<p>Horizontal Plane Cleavage (B)</p> Signup and view all the answers

What distinguishes basal progenitors from radial glial cells?

<p>Basal progenitors are not attached to the pial surface (D)</p> Signup and view all the answers

What role do radial glial cells play in the brain's ventricular zone?

<p>They drive the expansion of the ventricular zone (A)</p> Signup and view all the answers

What is a major result of asymmetrical division in radial glial cells?

<p>One daughter cell becomes a basal progenitor (C)</p> Signup and view all the answers

What is the primary purpose of tightly regulating cell cycle dynamics?

<p>To prevent premature depletion of progenitor pools. (B)</p> Signup and view all the answers

Which statement accurately describes thymidine analogues like BrdU and EdU?

<p>They substitute for thymidine in DNA synthesis during the S phase. (C)</p> Signup and view all the answers

What is the approximate percentage of cortical cells that comprise the population dynamics?

<p>5% (A)</p> Signup and view all the answers

What is the significance of the saturation point in cumulative labeling with thymidine analogues?

<p>It represents the maximum amount of tracer accumulated in the proliferative zone. (B)</p> Signup and view all the answers

What is a key assumption made when measuring cell cycle kinetics through cumulative labeling?

<p>Quiescent cells exit the proliferative zone and do not re-enter. (A)</p> Signup and view all the answers

How does the cell cycle length change with age according to in vivo observations?

<p>It slows significantly. (C)</p> Signup and view all the answers

What is the length of the cell cycle in vitro, as observed in the content?

<p>30-70 hours (B)</p> Signup and view all the answers

Why is measuring glial cell dynamics more challenging than measuring other cell types?

<p>They are dispersed throughout the tissue, complicating tracking. (B)</p> Signup and view all the answers

What percentage of adults express proliferation markers according to the single-cell RNA sequencing findings?

<p>~3% (B)</p> Signup and view all the answers

What do oligodendrocyte precursor cells (OPCs) differentiate into, and what is their primary function?

<p>They differentiate into oligodendrocytes that produce myelin. (B)</p> Signup and view all the answers

What is a key observation regarding human cell production in comparison to rodents?

<p>Cell production occurs primarily early in life. (B)</p> Signup and view all the answers

What would be a consequence of overproduction of progenitors in late development?

<p>Disruption of cell type balance. (A)</p> Signup and view all the answers

Which assumption is NOT needed when measuring cell cycle dynamics?

<p>All cells divide at the same time. (A)</p> Signup and view all the answers

What is the role of oligodendrocytes produced from OPCs in the nervous system?

<p>To generate myelin for saltatory conduction. (B)</p> Signup and view all the answers

In the double labeling protocol, what does the second injection of Edu indicate?

<p>It indicates cells still in S phase. (D)</p> Signup and view all the answers

Which of the following describes the primary consequence of lineage deletion of oligodendrocyte precursor cells?

<p>It is incompatible with life. (D)</p> Signup and view all the answers

What results from cells that have exited S phase in the double labeling protocol?

<p>They will show only BrdU incorporation. (C)</p> Signup and view all the answers

What trend is observed regarding the expression of proliferation markers in juveniles compared to adults?

<p>It is significantly higher in juveniles. (C)</p> Signup and view all the answers

Which tracer is injected first in the double labeling protocol?

<p>BrdU (A)</p> Signup and view all the answers

Flashcards

Prosencephalon (forebrain)

The most anterior part of the developing brain, giving rise to the cerebral hemispheres, thalamus, hypothalamus, retina, and other structures.

Telencephalon

A secondary vesicle of the prosencephalon that develops into the cerebral hemispheres containing the gray and white matter and plays a role in higher cognitive functions.

Diencephalon

A secondary vesicle of the prosencephalon that develops into structures like the thalamus and hypothalamus, playing roles in sensory integration, hormone regulation, and sleep-wake cycles.

Mesencephalon (midbrain)

The middle part of the developing brain forming the midbrain which involves motor control, visual and auditory functions.

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Rhombencephalon (hindbrain)

The posterior part of the developing brain, responsible for developing the pons, cerebellum, and medulla, which control vital functions, coordination, and balance.

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Metencephalon

A secondary vesicle of the rhombencephalon that develops into the pons and cerebellum, essential for motor control and coordination.

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Myelencephalon

A secondary vesicle of the rhombencephalon that develops into the medulla, which controls vital functions like breathing, heart rate, and blood pressure.

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Radial Glial Cells

These cells have long fibers extending from the inner lining of the brain (ventricular surface) to the outer layer (pial surface), acting as a guidance system for migrating neurons.

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Self-Renewal

Radial glial cells can divide to create more of themselves, ensuring a continuous supply for brain development.

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Neuron Production

Radial glial cells produce new neurons that travel along their fibers to their final destination in the brain.

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Transition to Astrocytes

Later in development, radial glial cells can transform into astrocytes, which support and protect neurons.

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Vertical Plane Cleavage

Early in brain development, radial glial cells divide vertically, creating identical copies of themselves to increase their numbers in the ventricular zone.

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Horizontal Plane Cleavage

Later in development, radial glial cells divide horizontally to create a radial glial cell and a basal progenitor, a specialized cell that produces neurons.

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Interkinetic Nuclear Migration (IKNM)

The nuclei of radial glial cells move rhythmically between the ventricular and pial surfaces during their cell cycle, dividing at the ventricular surface.

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Outer Radial Glial Cells (oRGCs)

These cells are found in the outer subventricular zone (OSVZ) and attach only to the pial surface, contributing to the growth of the cortex.

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oRGCs and Human Brain Complexity

Humans have a significantly larger number of oRGCs compared to other species, allowing for a more expanded and complex cortex.

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Cell Cycle Dynamics

The controlled progression of a cell through stages of growth, DNA replication, and division.

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Premature Depletion of Progenitor Pools

Avoiding the depletion of a cell population that is able to give rise to new cells.

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Overproduction of Progenitors

Preventing the excessive production of progenitor cells during development to maintain a balanced cell population.

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Thymidine Analogues

Substances that chemically resemble thymidine and can be incorporated into DNA during the S phase of the cell cycle.

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Cumulative Labelling

The process of measuring the rate at which cells divide by tracking the incorporation of thymidine analogues.

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S Phase

The phase of the cell cycle where DNA is replicated.

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G0 Phase

The part of the cell cycle where the cell is not dividing.

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Progenitor Cells

Cells that have the ability to give rise to different types of specialized cells.

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Oligodendrocytes

A type of glial cell in the brain that produces the myelin sheath that insulates nerve fibers.

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Oligodendrocyte Precursor Cells (OPCs)

Cells that are responsible for generating new oligodendrocytes.

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What are Oligodendrocyte Precursor Cells (OPCs)?

A type of neuron that continues to divide throughout life, crucial for brain plasticity and regeneration. They make up around 5% of cortical cells.

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What is cell cycle length?

The time it takes for a cell to complete one cycle of division, including phases like G1, S, G2, and M.

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What is cell proliferation?

The process of dividing and creating new cells from parent cells. It is essential for growth and development.

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How does cell cycle length differ in vivo and in vitro?

In vivo refers to studies conducted within a living organism, where cell cycle length slows down with age. In vitro refers to studies done in a controlled environment like a petri dish, where the cell cycle length remains shorter.

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What is the double labeling protocol?

A technique that uses two different thymidine analogues, BrdU and Edu, to measure the duration of the S phase (DNA synthesis) and cell cycle length.

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What is BrdU (Bromodeoxyuridine)?

A type of thymidine analog that gets incorporated into DNA during the S phase, allowing researchers to track cells that are actively replicating.

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What is Edu (5-ethynyl-2'-deoxyuridine)?

Another thymidine analog that gets incorporated into DNA during the S phase, used in conjunction with BrdU to calculate the duration of the S phase.

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What is the S phase?

A phase within the cell cycle where DNA replicates. This is the phase that both BrdU and Edu can be incorporated into.

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What is mitosis?

The process of actively dividing and creating new cells from parent cells.

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What is the G0 phase?

A state where cells are not actively dividing and are in a resting state.

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Outer Subventricular Zone (OSVZ)

The outermost region of the subventricular zone, expanding during human brain development to generate a larger cortex and increase cortical cell numbers.

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Expansion of the OSVZ in Human Development

During human brain development, the OSVZ increases significantly, leading to a more complex and larger cortex. This unique expansion distinguishes human brains from those of other species like mice.

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Cell Type Production from Ventricular Regions

This process involves the production of various types of neurons and glial cells from different regions of the ventricular surface. This regional patterning persists into adulthood, maintaining specific cell types.

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Morphogen Gradient in Brain Development

Morphogens are signaling molecules that create gradients, directing the development of the brain tube. These gradients pattern the brain by guiding cell production, ensuring the formation of the correct types of cells in the right locations.

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Study Notes

Neural Stem Cells, MS, and Parkinson's

  • The central nervous system (CNS) develops completely from the neural tube.
  • The peripheral nervous system (PNS) arises from the neural crest and cranial placodes.
  • The CNS is made up of the brain, brainstem, cerebellum, and spinal cord.
  • The PNS is made up of peripheral nerves and ganglia.
  • Sensory ganglia contain sensory neurons and glial cells.
  • Autonomic ganglia contain autonomic neurons and glial cells.
  • Neurons are the primary functional units of the CNS.
  • Glial cells provide support to neurons, including oligodendrocytes that produce myelin and astrocytes that contribute to the blood-brain barrier.
  • Ependymal cells line the ventricles. Microglia are innate immune cells of the CNS.
  • The neural crest gives rise to most of the autonomic nervous system, peripheral nerves and sensory neurons in spinal and cranial ganglia.
  • Cranial placodes contribute to cranial sensory ganglia and parasympathetic ganglia.
  • Primary vesicles include prosencephalon (forebrain), mesencephalon (midbrain) and rhombencephalon (hindbrain), which develop into secondary vesicles.
  • The ventricular system is made up of the lateral ventricles, third ventricle, cerebral aqueduct, fourth ventricle, and central canal.
  • The radial unit hypothesis suggests that stem cells in the ventricular zone produce neurons.
  • Cells migrate along radial glial fibres toward the outer cortical surface, resulting in the basic structural units of the cortex.
  • Zones of the developing cortex include the ventricular zone(VZ), intermediate zone(IZ), subplate(SP), cortical plate(CP), and marginal zone (MZ), all of which are vital for cortical development.
  • Additional cells like interneurons and glial cells migrate from other brain regions for column integration.
  • Radial glial cells extend from the ventricular surface to the pial surface (apical-basal).
  • Functions of radial glial cells include self-renewal through cell division, production of neurons that migrate along their fibres, and eventually transitioning into astrocytes contributing to the blood-brain barrier.
  • Modes of division in radial glial cells include vertical cleavage (symmetric division) and horizontal cleavage (asymmetric division).
  • Interkinetic nuclear migration (IKNM) describes how radial glial cells oscillate their nuclei between ventricular and pial surfaces during the cell cycle.
  • Outer radial glial cells (oRGCs) are unique to humans and attach only to the pial surface, differentiating and contributing to cortical growth.
  • Subventricular Zone (SVZ) and Outer Subventricular Zone (OSVZ) are important zones within the brain for stem cell functions.
  • Radial glial stem cells show a relationship between their nucleus position and the cell cycle phase (G1, S, G2, M, G0).
  • Cell cycle length regulation is crucial during development as it impacts progenitor pool expansion and neuron differentiation.
  • Cumulative labelling with thymidine analogues, such as BrdU or EdU, measures cell cycle kinetics by looking at the time-dependent incorporation of tracers.
  • Progeny in the GO phase can't be distinguished from dividing cells in tissue.
  • Different cell cycle lengths are noticeable across different regions in cells differentiating, impacting the diversity of cortical subtypes.
  • Morphogens, including Wnt, RA and Shh, help generate cell types.
  • As development goes further, B cells or adult stem cells lose the radial glial cell appearance but can still generate neurons.
  • In humans, the expansion of the outer subventricular zone (OSVZ) significantly increases cortical complexity during brain development.
  • Crystals labelled on the surface of the brain show differences in development and labelling with time.
  • Crystal labelling differentiates cells closer to the outer layers during development and later in development to cells closer to the outer radial glial cells (oRGs).
  • The labelling of cells in the inner surface remains throughout during development (VZ to pia).
  • Stem cells in the outer and inner subventricular zone are important for cortical generation in humans.
  • Stem cell differences exist in humans and mice based on how the regions develop.
  • Neural stem cells are important in modelling diseases and as therapeutic targets in diseases such as MS.
  • Key aspects include limitations in modelling diseases, ensuring precise target brain integration, and limitations in harvesting/maintaining stem cells.
  • Multiple sclerosis (MS) is an autoimmune disease attacking myelin. Myelin insulates axons enabling fast conduction and providing metabolic and trophic support to them. Myelin loss causes irreversible damage.
  • OPCs (oligodendrocyte precursor cells) are cells capable of producing new myelin.
  • Studies have shown that genetic modifications can encourage oligodendrocyte production (and myelin). Key transcription factors, specifically OLIG2, can enhance the production of myelin.
  • Stem cells are relevant in research that helps understand disease processes, producing different cell types from human stem cells, and creating human cells for transplantation, as well as in generating brain tissue models.

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