Neural Development Flashcards
How many connections do neurons make with other neurons?
About 1000
Phase 1 of neural development
Different cells types (neurons, glia, muscle cells) develop independently at widely separate locations in embryo according to local program and are unconnected. (Think differentiation and survival)
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.
Phase 3 of neural development
Continues into adult life, connections are adjusted and regained through interactions with distant regions via electric signals
What provides the supporting framework and nutrition to nuerons being produced?
Glial cells
What does neurons and glial cells develop from?
Ectoderm
CNS (brain, spinal cord and retina) is derived from?
Neural tube
PNS (nerves, sensory neurons) is derived from?
Neural crest
Formation of the neural tube
Derived from a single layered epithelium. Starts w/ neural groove on the dorsal side of the embryo that gradually deepens as nueral folds become elevated. Ultimately the folds meet and coalesce in the middle line and convert the groove into a closed tube (neural tube). Center of the tube is called the neural canal
What controls differentiation into neurons?
Delta Notch signaling (lateral inhibition)
Mechanism of delta notch in differentiation of neurons
Signal proteins secreted from ventral and dorsal side of NT act as opposing morphogens, causing neurons at different dorso-ventral positions to express different gene regulatory proteins
What is secreted from the roof plate of the neural tube?
BMP
What is secreted by the floor plate of the NT?
Shh (notochord secretes it too)
Where do neural crest cells originate?
Dorsal end of the neural tube
Closure of the neural tube =
Neurulation
Neural crest differentiation several differentiated cell types like:
Neurons and glial cells of the PNS; epinephrine-producing cells of the adrenal gland; many of the skeletal and CT components of the head
What does fate of the neural crest cells depend on?
Where they migrate to and settle
Describe the migration of neurons
Neurons migrate from their original birthplace and settle in a different location. After final division close to the inner face of the NT they crawl along radial glial cells which extend from inner to outer end of the NT
Dorsal neurons of spinal cord receive and relay sensory info from ______ neurons located _______?
Sensory neurons located in the periphery of the body
Ventral clusters of spinal cord neurons develop as __________ neurons
Motor neurons - send out long axons to connect w/ specific subset of muscles
Intermediate location has what?
Inter neurons that connect specific set. Of nerve cells to each other
Tip of axon/dendrite has an irregular, spiky enlargement called?
Growth cone - crawls through surrounding tissue, trailing the axon/dendrite behind. It has the engine and steering apparatus that directs the process along the right path.
One growth cone will start migrating fast and develop what?
Axon-specific proteins - will for the axon
Growth cone behavior is dictated by what?
It’s cytoskeletal machinery b/c they put out filopodia and lemelopodia
What controls the assembly/disassembly of actin filaments that control movement of the growth cone?
Monomeric GTPases Rho and Rac
What two major cues are exploited for growth cones to find their way?
- Extracellular matrix environment sensed by receptors present on membrane.
- Chemotactic factors released by neighboring cells.
Explain the meaning of contact guidance
Growth cones often follow a path taken by other cells (ex - nerve fibers are usually found in bundles)
Contact guidance in growth cones is mediated by?
Homophilic cell adhesion molecules
What are 2 important classes of homophilic cell adhesion molecules that mediate contact guidance in growth cones?
- Ig superfamily 2. Cadherin family
What matrix molecules favors axonal outgrowth?
Laminin
What matrix molecules INHIBIT growth?
Chondroitin sulfate proteoglycans
The first stage of commissural neuron guidance depends on secretion of what ligand?
Netrin - by cells of the floor plate
What is the outcome of netrin binding it’s recepto?
Opening of TRPC (transient receptor potential C) channels which allow entry of extracellular Ca, activating machinery for extension of filopodia and growth cone movement.
What don’t other cells migrate toward floor plate?
They don’t have netrin receptors like commissural neurons
What do midline cells secrete?
Slit
What is the receptor for slit and where is it found?
Roundabout. Present on commissural neurons
Function of slit
Repels growth cones and blocks entry to the midline.
What is the second repellant signal along with slit?
Semaphorin
What regulates which growth cones synapse and where?
Signal from the target tissue
What are the signals produced by the target cell called and what is their function?
Neurotrophic factors; needed for survival (if they don’t get enough they die by programmed death)
What was the first prototypical neurotrophic factor to be identified?
Nerve growth factor (NGF)
NFG Nerve Growth Factor
Belongs to the family of neurotrophins. Is a tyrosine kinase (TrkA). Promotes survival of specific sensory neurons and sympathetic neurons
Short term effects of NGF
Effect on growth cone and neurite extension. Effect is local, direct, rapid and independent of communication w/ cell body
Long term effects of NGF
Effect on cell survival. Mediated by its receptor, uptake into cells via endocytosis and stimulation of downstream signaling pathways
Synaptic remodeling is dependent upon what 2 rules that create spatial order?
- Axons from cells in different regions of retina (which are excited at differnt times) compete for tectal neurons.
- Axons from neighboring site which are excited at same time cooperate/collaborate to retain and strengthen synapses w/ tectal neurons
Activity dependent synaptic remodeling depends on what?
Electrical activity and synaptic signaling
Adult memory
Synapses are strengthened by external events that cause 2 or more neurons to be activated at the same time Entry of Ca through the glut receptor NMDA triggers lasting change in synaptic strength. Corresponding change in physical structure of synapse
How many neurons does the brain have?
10^11
