Source: A Brain-Mind Odyssey, UC Berkeley
Tags: genetic material, chromosomes, DNA, cell differentiation, transcription factors, neurogenesis, gliogenesis, synaptogenesis, growth cone, chemoaffinity hypothesis, neuroplasticity, synaptic pruning, Roger Sperry, Ramon y Cajal
Every cell in the human body carries the same genetic code, but different cells express different genes thanks to transcription factors and regulatory RNAs. The nervous system develops through a sequence of neurogenesis, gliogenesis, cell migration, and synaptogenesis, with axons guided to their targets by chemical signals. Once wired, synapses are continuously strengthened or weakened through presynaptic and postsynaptic mechanisms, a process known as neuroplasticity.
Diploid chromosomes
The full set of 46 chromosomes (23 pairs) found in most human cells, with one copy of each pair inherited from each parent.
Haploid chromosomes
A single set of 23 chromosomes, representing the genetic contribution from one parent.
Nucleotide base pairs
The molecular "letters" of DNA: adenine (A), thymine (T), guanine (G), and cytosine (C). Approximately 3 billion base pairs make up the human genome.
Cell differentiation
The process by which cells with identical genetic information become specialised for different functions. Begins hours after fertilisation.
Transcription factors
Proteins that bind to regulatory regions of DNA and control which genes are read out (transcribed) in a given cell.
Dark matter of the DNA
The roughly 97% of the human genome that does not code for functional protein. Much of it is transcribed into regulatory RNAs involved in gene expression.
Embryonic stem cells
Cells formed from the dividing fertilised egg that retain the capacity to differentiate into many different cell types.
Neurogenesis
The formation of new neurons from progenitor cells.
Gliogenesis
The formation of new glial cells from progenitor cells.
Synaptogenesis
The process by which maturing neurons wire together and form synaptic connections.
Neural tube
A structure formed roughly three weeks after conception by folding cells; the entire central nervous system develops from it.
Growth cone
The motile tip of a growing axon, which navigates toward its target using fingerlike extensions called filopodia.
Filopodia
Fingerlike projections at the tip of the growth cone, propelled by the cytoskeleton. Filled with microfilaments (actin).
Microfilaments
Cytoskeletal strands made of actin protein (375 amino acids each). Found within filopodia and throughout cells; involved in cell movement and growth.
Microtubules
Cytoskeletal strands made of alpha-tubulin and beta-tubulin proteins (each tubulin ~450 amino acids). Involved in intracellular transport, growth, and structural support.
Chemoaffinity hypothesis (Roger Sperry)
The proposal that nerve cells use specific chemical signals to guide their wiring during development and neural regeneration.
Nerve growth factor (NGF)
A protein molecule that regulates cell growth, differentiation, migration, and synaptogenesis. The first identified neurotrophin.
Neurotrophin
A family of growth-factor proteins that support neuron survival and development. Examples include NGF, BDNF, GDNF, and NT3.
Ephrin proteins
Cell-surface proteins involved in contact-based axon guidance; they bind to ephrin receptor proteins on neighbouring cells.
Synaptic pruning
The elimination of synapses that are not used, refining neural circuits over development.
Neuroplasticity
The capacity of synapses to be strengthened or weakened over time through presynaptic and postsynaptic mechanisms.
Every cell in the body carries the same genetic information: 46 diploid chromosomes (23 pairs), with approximately 3 billion nucleotide base pairs across those 23 chromosomes.
Only about 3% of the genome codes for functional protein. Roughly 85% of the genome is transcribed into RNAs.
Non-coding RNAs (the "dark matter" of DNA, comprising ~97% of the genome) play a crucial role in regulating gene expression.
Differentiation begins hours after fertilisation. Although every cell has the same DNA, different genes are transcribed and translated depending on the cell type.
This process is regulated by transcription factors, proteins that bind to regulatory regions of DNA and control which genes are expressed.
After conception, the fertilised egg divides to form embryonic stem cells, which can differentiate into many cell types.
The developmental sequence runs: neurogenesis → gliogenesis → cell migration → synaptogenesis.
At roughly three weeks, cells fold to form the neural tube, from which the entire central nervous system develops.
By the third month after conception, the gyri and sulci of the cerebral cortex begin to form (during the final two months before birth), reflecting the rapid expansion of cell density and connectivity.
Brain expansion is driven by: proliferation of neurons and glia from stem cells, growth and branching of dendrites and axons, and the formation of trillions of synaptic connections.
Examined the cellular morphology of developing neurons and described how axon tips extend and seek out connection points with other neurons.
Hypothesised that growing axon tips possess mechanisms of sensitivity, motility, and guidance.
The term "neurogeny" refers to the embryonic development of the nervous system.
The growth cone advances via filopodia, fingerlike extensions propelled by the internal cytoskeleton.
The cytoskeleton consists of: microfilaments (actin, 375 amino acids) and microtubules (alpha- and beta-tubulin, each ~450 amino acids).
These structures perform multiple functions: cell growth and movement, intracellular transport, insertion and removal of membrane proteins (e.g. ion channels).
Psychopharmacology note: drug molecules can enter cells and interact with intracellular structures like microfilaments, which may contribute to a drug's effects.
Sperry studied how neurons form connections, using frogs and salamanders (chosen for their regenerative capacity).
His key experiment: he cut the optic nerve of a frog and rotated the eyeball 180 degrees. After the nerve regenerated, the frog saw the world upside down and backwards, indicating the nervous system re-formed the same connections as before.
This led to the chemoaffinity hypothesis: nerve cells use specific chemical signals to guide their wiring during development and regeneration.
Nerve growth factor (NGF) was the first neurotrophin identified. Other neurotrophins include BDNF, GDNF, and NT3.
Axon guidance can also involve direct contact between cell-surface proteins, such as ephrin proteins binding to ephrin receptors on adjacent cells.
Synaptic connections form throughout the cerebral cortex; unused synapses are eliminated through synaptic pruning.
Neurogenesis continues in the hippocampus in adulthood, with roughly 1,400 new neurons added daily across both hippocampi.
Myelination continues past age 20, as it is needed for cortical neurons to communicate effectively.
Presynaptic strengthening: prolonging depolarisation in the axon terminal keeps voltage-gated Ca²⁺ channels open longer, leading to more vesicle fusion and greater neurotransmitter release. Presynaptic glutamate receptors can contribute by opening Na⁺ or Ca²⁺ channels that extend depolarisation.
Postsynaptic weakening (via retrograde signals): the postsynaptic cell sends retrograde signals to the axon terminal that influence gene transcription for reuptake transporter proteins. More reuptake transporters means neurotransmitter is cleared from the synaptic cleft faster, producing a smaller signal and a weaker synapse.
Postsynaptic receptor regulation: the postsynaptic cell can also influence gene transcription to produce more or fewer neurotransmitter receptors, which are then inserted into or removed from the postsynaptic membrane, changing synapse strength.
⚠️ Know the developmental sequence: neurogenesis → gliogenesis → migration → synaptogenesis.
⚠️ Be able to distinguish presynaptic from postsynaptic mechanisms of neuroplasticity, and explain how each strengthens or weakens a synapse.
⚠️ Sperry's frog experiment and the chemoaffinity hypothesis are classic exam topics. Understand both the method and the conclusion.
⚠️ Only ~3% of the genome codes for protein. The rest is not "junk" but largely regulatory RNA. This is a common exam mix-up.
⚠️ Microfilaments (actin) vs. microtubules (tubulin): know the structural difference and the protein each is made from.
Q: What is the developmental sequence from stem cells to functional neural circuits?
A: Embryonic stem cells → neuronal progenitor cells → neurogenesis and gliogenesis → cell migration → synaptogenesis.
Q: What did Sperry's frog experiment demonstrate, and what hypothesis did it support?
A: After cutting and rotating the frog's eye, the regenerated optic nerve re-formed the same connections as before, causing the frog to see the world upside down and backwards. This supported the chemoaffinity hypothesis: nerve cells use specific chemical signals to guide wiring.
Q: Describe one presynaptic mechanism that strengthens a synapse.
A: Prolonged depolarisation in the axon terminal keeps voltage-gated Ca²⁺ channels open longer, resulting in more vesicle fusion and increased neurotransmitter release into the synaptic cleft.
Q: How can the postsynaptic cell weaken a synapse via retrograde signalling?
A: The postsynaptic cell sends retrograde signals that influence gene transcription in the presynaptic terminal, increasing the number of reuptake transporter proteins. More reuptake transporters clear neurotransmitter from the cleft faster, reducing signal strength.
Q: What percentage of the human genome codes for functional protein, and what does the rest do?
A: About 3%. The remaining ~97% ("dark matter of the DNA") is largely transcribed into regulatory RNAs that play a crucial role in controlling gene expression.
Q: What is synaptic pruning?
A: The elimination of synapses that are not used. It refines neural circuits during development.
DNA, chromosomes, haploid, diploid, nucleotide base pairs, adenine, thymine, guanine, cytosine, transcription, translation, transcription factors, regulatory RNA, dark matter of DNA, embryonic stem cells, neural tube, neurogenesis, gliogenesis, synaptogenesis, cell migration, cell differentiation, Santiago Ramon y Cajal, neurogeny, growth cone, filopodia, cytoskeleton, microfilaments, actin, microtubules, tubulin, alpha-tubulin, beta-tubulin, Roger Sperry, chemoaffinity hypothesis, optic nerve, nerve growth factor, NGF, neurotrophin, BDNF, GDNF, NT3, ephrin, ephrin receptor, synaptic pruning, neuroplasticity, presynaptic, postsynaptic, retrograde signalling, reuptake transporter, voltage-gated calcium channels, myelination, hippocampus, psychopharmacology