Lecture 4: Neurodevelopment Flashcards
What was the idea of preformation?
- -Roman philosopher Seneca
- -Human embryo is a miniature version of an adult;
- -Development is just a process of getting bigger.
How did the idea of preformation fade out?
- -Preformation faded out as people realized embryos looked absolutely nothing like their adult counterparts;
- -Embryos of different species were more closely related than their respective parents;
- -Early in development, all embryos of vertebrate have common properties: head, some folds and a tail
What do the embryos of all vertebrates have in common?
–Young vertebrate embryos have a three-chambered brain:
1) Forebrain
2) Midbrain
3) Hindbrain
Remaining neural tube forms the spinal cord.
–Evidence for Darwin’s view that all vertebrates arose from a common ancestor
What happens on day 1 /2/15/21/49/100, 7 months and 9 months of neural development?
–day 1: Human zygote consists of a single cell (egg + sperm cell combine; fertilization)
–day 2: This cell divides and continues to divide.
–day 15: Emerging embryo is formed by several sheets of cells with a raised area in the middle called an embryonic disc (a raised area that results from cells building up on each other)
–day 21: Primitive neural tissue forms the neural plate, which gives rise to the neural tube. The neural plate folds into itself and forms a neural groove. Once this groove closes, it forms a neural tube. Cells in the neural tube are thought of as the nursery for the rest of the CNS! –where all the new neurons are born. This is true your entire life, the cells that line the neural tube continue to form neurons
Cylinder type space in the neural tube remains open;
Gives rise to the brain’s ventricles and the spinal canal.
–day 49: Embryo resembles a miniature person
–day 100: Brain begins to resemble that of a human.
–7 months: Formation of gyri and sulci.
–9 months: Very distinct human brain, although cellular structures is still much different than adult brain. However, although the brain looks like an adult brain, it is very functionally different - things are upside down and backwards. Things that would excite neurons at 9 months inhibit neurons as an adult, and vice versa.
What are neural stem cells?
- Multipotential cell; can become any type of cell
- Lining the neural tube;
- Extensive capacity for self renewal; –the stem cells can keep themselves alive by constantly renewing, and the new divided cell will be able to divide as well (unlike progenitor cells)
- In adults, neural stem cells line the ventricles forming the sub ventricular zone;
- Neural stem cells divide into progenitor cells (aka precursor cells).
What are progenitor cells and what do they divide into?
Progenitor cells can also divide; however they eventually produce non-dividing cells:
- Neuroblasts: develop into mature neurons after migration;
- Glioblasts: develop into mature glia.
What did Sam Weiss discover?
–Discovered that stem cells remain capable of producing neurons (neurogenesis) and glia throughout adulthood and even in an aging brain. We are constantly producing new neurons all day everyday which is why our brains are “plastic” because you can mold the brain like you can mold plastic. Neurogenesis happens all over the brain
Why are neurons in the adult brain not replaceable?
–because these neurons have to make the same connections as the old neurons did which is hard, if not impossible. With brain disorders that involve dysfunctional neurons, you can’t just insert neural stem because they can die as well. This is because the environment is toxic (there is an underlying issue that caused the dysfunction of the original neurons in the first place)
How do stem cells/progenitor cells mature into neurons/glia?
Newborn cells use chemical signals & genetic instructions throughout the developmental process.
1) Prolactin; female sex hormone, produced in the anterior pituitary, stimulates neurogenesis, spikes around pregnancy (to help form neurons in the baby’s brain).
2) Gene transcription; translating the correct genes that dictate a stem cell will become a neuron and not a skin cell, for example;
3) Epigenetics
- Different cells have different gene expression, leading synthesis of different proteins and ultimately different phenotypes;
- DNA methylation: a methyl group is attached to the DNA to turn off gene transcription (aka gene silencing);
- Different methylation patterns are needed to trigger the differentiation of stem cells;
- Methylation patterns are influenced by neighbouring cells, chemicals (e.g. hormones), stress, etc.
- these methyl groups ensure that the cell isn’t transcribing a gene that is meant for a different type of cell (ex. liver cell)
BPA –DNA methyl-transferase: picks methyl groups and transfers them to other parts of the DNA meaning a gene that is not meant to be expressed can get expressed and a gene that is supposed to get expressed is not
What are neurotrophic factors?
Chemical compounds that act to support growth and differentiation of neurons;
Keeps adult neurons alive and healthy;
1) Epidermal Growth Factor (EGF) stimulates stem cells to produce progenitor cells;
2) Basic Fibroblast Growth Factor (bFGF) stimulates progenitor cells to produce neuroblasts. Neuroblasts serve as an all-purpose neuron until they are exposed to certain growth factors in other areas.
What are the 7 neurodevelopment stages?
1) Cell Birth: neurogenesis, gliogenesis;
– Largely complete by 5 months (prenatally);
– During this time (0-5 months), brain is resilient to injuries (i.e. teratogens: something that can alter development of the brain) and/or trauma; this is because you have way more neurons that you will ever use
–Note: resilient ≠ resistant.
2) Cell Migration: traveling to final destination;
– Begins just after neurogenesis is complete; Lasts for ~6 weeks.
– cell has to travel to where it is needed (visual cell going to occipital lobe)
– How do neurons know when to stop? (i.e. cortical thickness)
the idea is through chemical signals but otherwise we don’t know
3) Cell Differentiation: developing specific tools/skill set;
–Begins during migration, continues after migration is complete; More-or-less complete at time of birth.
4) Cell Maturation: dendritic development, axonal growth;
– takes a long time, well into adulthood (25 years)
5) Synaptogenesis: formation of synapses;
– Each neuron begins forming its own networks; Can synapse with hundreds of thousands of other neurons;
6) Cell Death: apoptosis/pruning;
If you don’t use it, you lose it;
7) Myelogenesis: formation of myelin sheath
–there’s no point in myelinating a neuron that isn’t being used so this is why myelination is the last step
–Neuronal networks become more efficient in their communication; Sign of neurodevelopmental maturity; Occurs well into adulthood;
–Early-myelinating areas control simple movement, while late-myelinating areas (frontal lobe) control highest mental function
How do cells migrate and differentiate?
–Subventricular Zone (SVZ)
SVZ contains a primitive map of the cerebral cortex;
Cells formed in certain regions of the SVZ migrate to certain cortical locations.
– Radial Glial Cells
Form a path that extends from the SVZ to the surface of the cortex;
Undifferentiated progenitor cells follow this path.
–Intercellular signals progressively restrict the choice of traits a cell can express.
as the cell is migrating, it’s continuously differentiating itself based on signals from local environments (chemicals that make the cell turn on or off some genes through methylation)
these chemicals (intercellular environment) will be released at a specific time so the cell has to be there when it is released (timing)
Therefore, the emergence of a cell type is a combination of genetic instructions, timing and signals from neighbouring cells in the local environment.
– Cortical layers form from inside out. The most inner layer (VI) are first to form.
How are dendrites/axons formed to develop synapses?
1) Dendrites to provide surface area for synapse formation:
Branching of dendrites (arborization);
Growth of dendritic spines (one micrometer a day).
2) Axon extending to appropriate target to initiate synapse formation
Occurs very rapidly (one millimeter per day);
Various molecules attract or repel axon tip, thus guiding it through a very complex terrain.
– Growth Cones: growing axons
– Filopod: Growth cones extend shoots called filopod (e.g. fingers on a hand);
These filopods are like chemical sensors so they’re scanning the environment for particular chemicals. Some chemicals are attracting these filopods while others are repelling. The ones that attract will then cause the axon to turn towards that direction
growth cones/filopods are responsive to..
1) Cell-adhesion Molecules (CAMs)
Secreted from cells or lie on cell surface; help cells stick to each other
2) Tropic Molecules Secreted from target cells; Carry “come here” or “go away” message; Netrin (L. to guide) is the only known group.
How do synapses develop?
- At 7th gestational months, these connections are rather simple;
- At birth, the number of synapses increases dramatically;
- By 2 – 4 months, the number of synapses in the visual cortex doubles, and continues to increase for years –as the number and complexity of synapses increases, then the ability of vision increases
Why does synaptic pruning happen?
– we start with too many neurons and too many synapses at birth. Development is figuring out which synapses/cells you need, and which ones you don’t need (depending on what neurons or used or not used)
– Neural Darwinism: Environmental pressure leads to competition amongst neurons.
– apoptosis: programmed cell death (things are broken down and recycled)
– Genetics signals, experience, hormones, stress, etc. are all factors that can initiate apoptosis;
–The exception to this is in language centers
Unique role of language processing and nature of language-learning processes makes this area an exception to this rule. –more neurons get added because as you grow up you learn more words
–pruning occurs even when you get older but its as a function of maintenance rather than neurodevelopment
