Development of Multicellular Organisms II: Neural Development Flashcards
How many neurons does the brain have?
1x10^11 neurons
The brain has 1x10^11 neurons, with each neuron making connections with how many other neurons?
about 1000 other neurons
How many phases are there in neural development?
3 phases
What happens in phase 1 of neural development?
Different cell types (neurons, glia, muscle cells) develop independently at widely separate locations in embryo according to local program and are unconnected.
** genesis of neurons **
What happens in phase 2 of neural development?
Axons and dendrites grow out along specific routes setting up a provisional but orderly network of connections between various parts of the system.
** outgrowth of axons and dendrites **
What happens in phase 3 of neural development?
continues into adult life, connections are adjusted and refined through interactions with distant regions via electric signals.
** refinement of synaptic connections **
What other cell type in the nervous system are neurons produced in association with?
Glial Cells (provide supporting framework and nutrition).
What do are both neurons and glial cells developed (derived) from?
Ectoderm - from a common precursor.
What makes up the central nervous system?
- brain
- spinal cord
- retina
What structure is the central nervous system derived from?
neural tube
What make up the peripheral nervous system?
- nerves
- sensory neurons
What structure is the peripheral nervous system derived from?
neural crest
True or False:
The neural tube is derived from a mutli-layered epithelium.
False - neural tube is derived from a single layered epithelium.
What does the formation of the neural tube start with?
Starts with a neural groove on the dorsal side of the embryo.
What is formed as the neural groove gradually deepens during neural tube formation?
Neural folds become elevated as the the neural groove gradually deepens.
What ultimately happens in neural tube formation when the neural folds meet and coalesce in the midline?
Ultimately the neural folds meet and coalesce in the middle line and convert the groove into a closed tube, the NEURAL TUBE.
What is the center of the neural tube called?
Neural Canal
What signaling mechanisms (and ligand) controls differentiation into neurons in the neural tube?
Delta Notch signaling (lateral inhibition).
- Delta is the ligand **
- Notch is the receptor **
Signal proteins secreted from ventral and dorsal side of neural tube act as opposing morphogens. What does this cause?
Causes neurons at different dorso-ventral positions to express different gene regulatory proteins.
What morphogen is secreted by the roof plate and adjacent cells of the neural tube?
BMP proteins
important in production of extracellular matrix and pattern formation
What morphogen is secreted by the floor plate and notocord of the neural tube?
Sonci Hedgehog protein
At which end of the neural tube does neural crest cells originate?
dorsal end
At what point do neural crest cells migrate extensively to generate several differentiated cell types?
Migrate extensively during or shortly after closure of the neural tube or neurulation.
What are the several differentiated cell types that are generated by neural crest cells?
- Neurons and glial cells of the PNS.
- Epinephrine-producing cells of the adrenal gland.
- Many of the skeletal and connective tissue components of the head.
What does the fate of neural crest cell differentiation depend on?
Where they migrate to and settle.
After final division close to the inner face of the neural tube, how do neurons migrate?
Crawl along radial glial cells.
- radial glial cells extend from inner to outer end of the neural tube *
In the development of the spinal cord, what modulates the characteristics of neurons and the connections they make?
Differences in Gene Expression
What neurons of the spinal cord receive and relay sensory information from sensory neurons located in the periphery of the body?
Dorsal Neurons
What do ventral clusters of spinal cord neurons develop as?
Motor neurons - send out long axons to connect with specific subset of muscles.
What type of neurons are found in the intermediate location within the spinal cord?
Inter-neurons - that connect specific set of nerve cells to each other.
What is the composition of a typical immature neuron?
- cell body
- long axon
- several short dendrites
What is a “growth cone”?
Tip of axon/dendrite has an irregular, spiky enlargement - called growth cone.
What is the tip of an axon/dendrite that has an irregular, spiky enlargement called?
Growth Cone
growth cone crawls through surrounding tissue, trailing the axon or dendrite behind
True or False:
The growth cone at the tip of a axon/dendrite crawls through surrounding tissue, trailing the axon or dendrite behind and has the engine and steering apparatus that directs the process along the right path.
True
What is formed once the growth cone starts migrating fast and develops axon-specific proteins?
Axon is formed.
What machinery dictates growth cone behavior?
Cytoskeletal machinery
they through out filopodia and lamelopodia
What controls the assembly/disassembly of actin filaments, which control movement of growth cone?
Monomeric GTPases Rho and Rac.
What phase of neural development are we in during migration of the growth cones?
Phase 2
In the migration of growth cones, what two major cues are are used to find their way?
- Extracellular matrix environment sensed by receptors present on membrane.
- Chemotactic factors released by neighboring cells.
What is contact guidance?
The growth cones often follow a path taken by other cells.
** consequently, nerve fibers are usually found in bundles **
What is contact guidance mediated by?
homophilic cell adhesion molecules
What are the two important classes of homophilic cell adhesion molecules that mediate contact guidance in the migration of growth cones?
- Immunoglobulin superfamily
- Cadherin family
What do homophilic cell adhesion molecules provide a mechanism for?
Selective guidance and recognition - for migration of growth cones (contact guidance).
What matrix molecule favors axonal outgrowth?
laminin
What matrix molecule inhibits growth?
chondroitin sulfate proteoglycans
What are the two signals in which chemotactic factors can send?
- attractive
- repulsive
Examples:
> Netrin - attractant
> Slit - repellent
> Semaphorin - repellent
What does the first stage of the commissural neuron guidance mechanism depend on?
Secretion of NETRIN by cells of the floor plate.
In the mechanism of commissural neuron guidance, what cells secrete netrin (attractant)?
Cells of the floor plate.
What does the binding of netrin to its receptor cause?
Opening of TRPC (transient receptor potential C) channels.
this allow entry of calcium
Nectin binding to its receptor causes the opening of TRPC channels, which allow entry of extracellular calcium. What does this influx of calcium activate?
Activation of machinery for extension of filopodia and movement of the growth cone.
True or False:
Non-commissural neurons in the neural tube also have netrin receptors, thus, allowing them to migrate towards the floor plate.
False - Non-commissural neurons in the neural tube do NOT have netrin receptors, so they do NOT migrate towards the floor plate.
In the mechanism of commissural neuron guidance, what chemotactic molecule is secreted by midline cells?
Slit (repellent)
- slit repels growth cones and blocks entry to the midline *
What is the function of the chemotactic molecule slit?
Repels growth cones and blocks entry to the midline.
Growth cones become sensitive to another repulsive signal called semaphorin. What does this cause the growth cones to do?
They become trapped between 2 sets of repellants (slit and semaphorin), which causes the growth cones to travel in a narrow track.
What regulates which growth cones synapse and where?
signal from target tissue
True or False:
Unidirectional signaling in nerve cells but in developing cells are bidirectional.
True
True or False:
Most neurons are made in excess and up to 50% die after they reach the target cell.
True
True or False:
Target cell produces limited amount of specific neurotrophic factors needed for survival.
True
those that do not get enough die by programmed cell death
Can be reversed by increasing number of target cells and exacerbated by decreasing number of target cells
What was the first prototypical neurotrophic factor to be identified?
Nerve Growth Factor (NGF)
What family does nerve growth factor (NGF) belong to?
Neurotrophins
What type of a receptor is the NGF receptor?
tyrosine kinase (TrkA)
What does nerve growth factor (NGF) promote?
Survival of specific sensory neurons and sympathetic neurons.
What are the short term effects of NGF?
Effect on growth cone and neurite extension.
Effect is local, direct rapid, and independent of communication with cell body.
What are the long term effects of NGF?
Effect on cell survival.
Mediated by its receptor, uptake into cells via endocytosis and stimulation of downstream signaling pathways.
What are the 2 rules that synaptic remodeling is dependent on for creating spatial order?
(1) Axons from cells in different regions of retina (which are excited at different times) compete for tectal neurons.
(2) Axons from neighboring sites which are excited at same time cooperate/collaborate to retain and strengthen synapses with tectal neurons.
What does activity-dependent synaptic remodeling depend on?
Electrical activity and synaptic signaling.
Neurons that fire together wire together.
What action strengthens synapses?
External events that cause 2 or more neurons to be activated at the same time.
What effect does calcium have on synaptic strength?
Entry of Calcium through the glutamate receptor (NMDA receptor) triggers lasting change in synaptic strength.
> This causes corresponding change in physical structure of synapse.
> Individual dendritic spines remodeled, new spines appear with electrical stimulation.
