EXAM3 - development of multicellular organisms II Flashcards
Neural development
What are the phases of neural development?
- phase 1
- different cell types develope independently at widely separate locations in embryo according to local program and are unconnected
- Phase 2
- Axons and dendrites grow out along specfic routes setting up a provisional but orderly network of connections between various parts of nervous system
- Phase 3
- continues into adult life adult life, connections are adjusted and refined thrpugh interactions with distant regions via eletric signals
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What is the origin of nervous system?
- Neurons are produced in association with glial cells (provide supporting framework and nutrition)
- Both cell types develope form ectoderm
- CNS = brain, spinal cord, and retina = NEURAL TUBE
- PNS = nerves, sensory neurons = NEURAL CREST
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How is the neral tube formed?
- Dervived from a single layer of epithelium
- starts with a neural groove on the dorsal side of embryo
- gradually deepens as neural folds become elevated
- the fold meet and coalesce in the middle line and convert the groove intoa a close NEURAL TUBE
- the center of the neural tube is the neural canal
How does signaling and the neural tube relate to one another?
- Delta notch signaling controls differentiation into neurons (lateral inhibition and positive feedback)
- Signal proteins secreted from ventral and dorsal side of neural tube act as opposing morphogens causing neurons at different dorso-ventro positions to express different gene regulatory proteins
- Neurons continue to generate to give rise to greater diversity
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What is BMP and Snoic hedgehog proteins?
- Bone morphogenic protein “BMP” - key in pattern formation, differentiation, secretion of extracellular matrix
- Sonic hedgehog protein - depends on proteoglycans for functions, activate latent genes , and transcription regression to activation
- BOTH ARE MORPHOGENS THAT CAN OPPOSE EACH OTHER
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How is the neural crest formed?
- Neural crest cells originate at the dorsal end of the neural tube
- Mirgrate extensively during or shortly after closure of the neural tube or neuralation
- generation of several different cell types
- neurons and glial cells of PNS
- EPinephrine-producing cells of adrenal gland
- many of the skeletal and connective tissue componets of the head
- fate of the neural crest cells depends on where they mirgrate to and settle
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How do neurons migrate ?
- Radial glial
- acts as a Scaffold and extend to other end
- Migrating neuron
- crawls on the radial glial
What is the molecular mechanism of neural migration
- A typical immature neuron has a cell body, long axon and several short dendrites
- Tip of axon / dendrite has an irregular spikey enlargement called growth cone
- Growth cone crawls through surrounding tissue while the axon or denrite trails behind
- One of the growth cone starts migrating fast and develops axon specfic proteins - this will form axon
What is are the characteristics of growth cones?
- Growth cones behavior is dictated by its cytoskeletal machinery
- growth cones move via filopodia and lamelopodia
- monomeric GTPases RHo and RAC control the assembly/dissassenbly of actin filaments which control movement of growth cone
- Growth cones withdraw cells from unfavorable surfaces and steer them towards favorable ones where they persist for longer time
What is growth cone migration?
- Growth cones travel towards target cells along predictable routes
- exploit two major cues to find their way
- extracellular matrix environment; sensed by receptors present on membrane
- chemotactic factors released by neighboring cells
- can be attractive or repulsive
How are the extracellular matrix and growth cones related?
- Growth cones often follow a path taken by other cells - contact guidance
- cause nerve fibers to be found in bundles
- Mediated by homophilic cell adhesion molcules
- two clases
- immunogloblin superfamily
- cadherin family
- MAtrix molecules favor axonal outgrowth
- laminin
- or like Chondroitin sulfate proteins they can inhibit growth
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How did the spinal cord relay and recieve information?
- Dorsal neurons of spinal cord recieve and relay sensory informaton from SENSORY NEURONS located in the periphery of the body
- Ventral clusters of spinal cord neurons develope as MOTOR NEURONS send out long axons to connect with specificsubset of muscles
- INtermediatie location has INTER_NEUURONS that connect specific set of nerve cells to each other
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What are chemotactic factors?
- Secreted by cells, act as guidance factors at strategic points along path
- may be attractive or repulsive
- examples
- netrin
- slit
- semaphorin
What is netrins role in the commissural neuron guidance?
- First stage depends on secretion of netrin by cells of the floor plate
- binding of netrin to its receptor causes opening TRPC (transient receptor potential C) channels
- allow entry of extracellular calcium
- leads to activation of machery for extension of filopodia and movement of growth cone
- Non commissural neurons neural tube do not have netrin receptors so do not migrate towards floor plate
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Where do Slit and semaphorin come into play during commissural neural guidance
- Midline cells secrete slit
- slit receptor Roundabout present on commissural neurons
- slit repels growth cones and blocks entry t the midline
- growth cones become sensitive to another repulsive signal called semaphorin
- trapped between 2 sets of repellants growth cones travel in a narrow track
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What are neurotrophic factors
- Signal from target tissue regulate which growth cones synapse and where
- once axonal growth cones reach eventual target cells. They then Halt, communicate, and make sunapses with target cells
- Most neurons are made in excess
- Target cells produces limited amount of neurotrophic factors needed for survival
- those that do not get enough die by programmed cell death
What is NGF?
- First neurotrophic factor was Nerve Growth Factor (NGF)
- Belongs to Neurotrophins
- Receptor for Tyrosine Kinase (TrkA)
- Promotes survival of specfific sensory neurons and sympathetic neurons
What are the effects of NGF?
- Short term
- effect on growth cone and neurite extension. Effect is ocal, direct, rapid and independt of communication with cell body
- long term
- effect on cell survival mediated by its receptor, uptake into cells via endocytosis and stimulation of downstream signaling pathways
What activity dependent synaptic remodeling?
- Each axon intitally branches widely and makes multiple synapses with target cell
- profusion of weak synapsese
- network subsequently trimmed by elimination of synapses and retraction of axon branches
- accompanied by sprouting of axons to develope denser distribution of synapses that survive
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Synaptic remodeling = depending upon 2 roles that create spatial order
- axons from cells in different regions of retina compete for tectal neurons
- axons from neighboring sites which are excited at same time cooperate/collaborate to retain and stengthen synapses with tectal neurons
- Activity Dependent = synaptic remodeling depends on eletrical activity and synaptic signaling
- Ex: retinal / tectal neurons
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What is the selectivity of retinal neurons for tectal position?
- Posterior retinal neuron axons prefer anterior tectal neurons
- anterior retinal neurona have no preference
- this occurs because the protein EphA occurs in the retinal posterior
- (EPhrinA) is in the tectal posterior prevents association with retina posterior
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How does the rule “neurons that fire together wire together also apply to the adult brain?
- Synapses are strengthed by external events that cause 2 or mre neurons to be activated at the same time
- entry of calicum through the gutamate receptor (NMDA RECEPTOR) triggers lasting change in synaptic strength
- corresponding change in physical structure of synapse
- indivdual dendrite spines remodeled, and new spines appear
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