Source: A Brain-Mind Odyssey, Ch. 10
Tags: neural development, neurogenesis, gliogenesis, neural tube, growth cone, chemoaffinity, neurotrophin, NGF, synaptogenesis, apoptosis, synaptic pruning, neuroplasticity, hippocampus, adult neurogenesis, stem cells, transcription factors
The nervous system develops from a simple tube of cells into an extraordinarily complex network through a tightly regulated sequence: cell division, differentiation, migration, axon guidance, synapse formation, and then selective pruning. This process does not stop at birth. The brain retains the capacity to rewire itself (neuroplasticity) throughout life, and limited neurogenesis continues in specific adult brain regions, notably the hippocampus and the subventricular zone.
Embryonic stem cell
A cell capable of continued division and differentiation into any cell type in the body. Directed by exposure to soluble contact factors and growth factors.
Neural progenitor cell
A cell committed to the neural lineage, able to become any of various types of neurons or glia, but not other body cell types.
Transcription factor
A protein that binds to specific DNA regions and regulates the expression of numerous genes. Controls which proteins a cell makes, thereby driving cell differentiation.
Neurogenesis
The formation of new neurons from neural progenitor cells.
Gliogenesis
The formation of new glial cells from neural progenitor cells.
Neural tube
The embryonic structure, formed within roughly three weeks of conception, from which the entire CNS develops.
Growth cone
The flared, motile tip of a growing axon. Extends via finger-like projections called filopodia. First described by Santiago Ramón y Cajal.
Filopodia
The finger-like extensions at the tip of a growth cone that sense the surrounding environment and guide axon growth.
Chemoaffinity hypothesis
Roger Sperry's proposal that nerve cells use specific chemical signals to guide their wiring during development and neural regeneration.
Neurotrophin
A protein that promotes the growth or survival of neurons. NGF (nerve growth factor) was the first to be discovered.
Apoptosis
Programmed cell death. A normal developmental process in which 50% or more of neurons in some brain regions are selectively eliminated.
Synaptic pruning
The elimination of synapses that are not sufficiently active. Activity stabilises synapses; disuse leads to their removal.
Neuroplasticity
The capacity of neural circuitry to alter its properties throughout life, through changes in synaptic strength, new connections, or structural remodelling.
46 chromosomes (23 from each parent); 23 = haploid, 46 = diploid
Approximately 3 billion nucleotide base pairs (adenine, thymine, guanine, cytosine)
Codes for roughly 21,000 proteins
Only about 2% of the genome is translated into functional protein
Most of the remaining 98% is transcribed into RNA (sometimes called the "dark matter" of the genome)
Embryonic stem cells can become any cell type
Exposure to growth factors and contact factors directs them toward specific fates
Neural progenitor cells are on track to become neurons or glia
Differentiation is governed by transcription factor proteins and RNA regulation
Transcription factors read DNA and produce matching mRNA
Different combinations of transcription factors cause cells to make different proteins, becoming different cell types
Neurogenesis: progenitor cells become neurons
Gliogenesis: progenitor cells become glia
Both occur alongside axon and dendrite branching
Forms within about three weeks of conception
A group of cells folds inward to create a tube
The entire central nervous system develops from this structure as it grows and differentiates
Growth cone (Cajal): the motile, flared tip of a growing axon
Extends filopodia that sense the environment
Cajal proposed it possessed mechanisms of sensitivity, motility, and guidance
Cytoskeleton drives the physical extension of axons and dendrites
Microfilaments: polymers of actin protein, ~7 nm diameter
Microtubules: polymers of tubulin protein, ~25 nm diameter; essential for growth, movement, and intracellular transport; composed of alpha and beta subunits
Chemical guidance of axon growth involves four categories:
Contact factors that attract (touch the axon and pull it toward)
Contact factors that repel
Soluble factors that attract (diffuse through fluid)
Soluble factors that repel
Example: Ephrin receptor interaction can mediate either attraction or repulsion depending on context
1930s-1940s experiments with frogs and salamanders (which can regenerate optic nerves)
Cutting the optic nerve in a frog caused blindness, but the nerve regrew and vision returned
Rotating the eyeball 180° caused the frog to see the world upside down and backwards
Rotating the eyeball and cutting the optic nerve: the frog still saw the world inverted after regrowth, because the axons formed exactly the same connections as before
Conclusion (chemoaffinity hypothesis): nerve cells use specific chemical signals to guide their wiring. Connections are not random; they are chemically specified.
NGF (nerve growth factor): the first neurotrophin discovered
Rita Levi-Montalcini and Stanley Cohen discovered it (Nobel Prize)
BDNF (brain-derived neurotrophic factor): another major neurotrophin
Neurotrophins are proteins produced by the body that promote neuron growth or survival
Guidance molecules involved in axon and dendrite pathfinding include ephrin, netrin, neuropilin, plexin
Some work by direct cell-to-cell contact (e.g., ephrin); others are soluble
Synaptogenesis: in the year following birth, vast numbers of synaptic connections form across the cerebral cortex
This is followed by an overproduction of cells and then apoptosis (programmed cell death)
50% or more of neurons may be eliminated in some regions
Synaptic pruning: synapses that are not used are eliminated
Activity determines which synapses survive
The more a synapse is used, the more stabilised it becomes
The brain's capacity to alter its neural circuitry throughout life
Operates through both presynaptic and postsynaptic mechanisms:
Presynaptic mechanism (strengthening)
Example: prolonging depolarisation in the axon terminal so voltage-gated Ca²⁺ channels stay open longer
More vesicles fuse with the membrane, more neurotransmitter is released
Result: stronger synapse
Postsynaptic mechanism (weakening)
Example: influencing transcription/translation of genes coding for presynaptic reuptake transporters
More reuptake transporter proteins means neurotransmitter is removed from the cleft faster
Result: weaker signal, weaker synapse
Postsynaptic mechanisms can also strengthen synapses (e.g., inserting more receptors)
Neuroplasticity is fundamental to learning and memory
Most neurons are produced between 5 weeks and 5 months of embryonic development
However, stem cells persist in the adult brain
Dentate gyrus of the hippocampus: a major site of adult neurogenesis
The dentate gyrus is a curved ridge within the hippocampus
Subventricular zone (lining the lateral ventricles): another site
New neurons born here migrate to the olfactory bulb
Likely serves to maintain olfactory function throughout life
Hippocampus: bilateral structure beneath the temporal lobe surface
Pivotal role in formation and stabilisation of memories
Primary structure for adult neurogenesis from precursor cells
Adult neurogenesis occurs in the olfactory epithelium (peripheral nervous system)
New olfactory neurons allow the sense of smell to be maintained across one's lifespan
⚠️ Know the sequence: neural tube → progenitor cells → neurogenesis/gliogenesis → axon guidance → synaptogenesis → apoptosis → synaptic pruning. Each step is testable.
⚠️ Sperry's chemoaffinity hypothesis is a classic experiment. Be able to describe the rotated-eye frog experiment and what it demonstrated.
⚠️ Distinguish neurogenesis (new neurons) from gliogenesis (new glia) from synaptogenesis (new synapses).
⚠️ Know the two adult neurogenesis sites: dentate gyrus of the hippocampus and subventricular zone (→ olfactory bulb).
⚠️ Neuroplasticity can strengthen or weaken synapses via presynaptic or postsynaptic changes. Be ready to give an example of each direction.
⚠️ Apoptosis is not pathological; it is normal, programmed developmental pruning.
Q: What is the chemoaffinity hypothesis, and what experiment led to its formulation?
A: Roger Sperry proposed that nerve cells use specific chemical signals to guide their wiring. He demonstrated this by rotating a frog's eyeball 180° and cutting the optic nerve. When the nerve regrew, the frog still saw the world upside down and backwards, indicating that axons reformed the same chemically specified connections regardless of the eye's orientation.
Q: Describe one presynaptic mechanism and one postsynaptic mechanism of neuroplasticity.
A: Presynaptic (strengthening): prolonging depolarisation at the axon terminal keeps voltage-gated Ca²⁺ channels open longer, causing more vesicle fusion and greater neurotransmitter release. Postsynaptic (weakening): upregulating reuptake transporter proteins on the presynaptic membrane removes neurotransmitter from the cleft faster, weakening the signal.
Q: Where does adult neurogenesis occur, and what is the functional significance of each site?
A: In the dentate gyrus of the hippocampus (linked to memory formation) and in the subventricular zone near the lateral ventricles (new neurons migrate to the olfactory bulb to maintain the sense of smell).
Q: What is apoptosis, and why is it important in neural development?
A: Apoptosis is programmed cell death. During development, an overproduction of neurons is followed by selective elimination of those that are not needed. Up to 50% or more of neurons in some regions undergo apoptosis. This refines the neural circuitry.
Q: What is the role of transcription factors in cell differentiation?
A: Transcription factors are proteins that bind to DNA and regulate gene expression. By activating or silencing different genes, they control which proteins a cell produces, thereby determining what type of cell it becomes.
neural development, neural tube, embryonic stem cell, neural progenitor cell, transcription factor, neurogenesis, gliogenesis, growth cone, filopodia, Cajal, cytoskeleton, microfilaments actin, microtubules tubulin, Roger Sperry, chemoaffinity hypothesis, ephrin, netrin, neurotrophin, NGF nerve growth factor, BDNF, Rita Levi-Montalcini, Stanley Cohen, synaptogenesis, apoptosis programmed cell death, synaptic pruning, neuroplasticity, presynaptic postsynaptic mechanisms, adult neurogenesis, dentate gyrus, hippocampus, subventricular zone, olfactory bulb, olfactory epithelium regeneration