early brain development part two
TRANSCRIPT
Growth cones
Growth cone has flat lamminar type of appearance: LAMELLA PODIUM (SHEET FLOOR).
FILOPODIA are processes that extend from the lamella podium.
Filopodia have dynamic behavior because they have ACTINS.
Growth cone is rich of mitochondria and it is very important for the axon development.
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Growht cone
https://cmgm.stanford.edu
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Molecular signals for axon guidance
cell-associated molecules
diffusible molecules
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Cell-associated molecules
Those molecules are on the surface of cells or embedded in extracellular matrix.
They mediate molecular interactions between growth cones and parenchyma.
Interactions with growth cone can trigger second messenger systems in growth cones that transduce extracellular signals
into patterns of growth.
These molecules are important for stabilizing linkages between axons and glia.
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Cell-associated molecules
integrins (extracellular matrix molecules)
calcium independent cell adhesion molecules (CAM) like NCAM and L1
calcium dependent cell adhesion molecules (CAM) like CADHERINS
EPHRINS and EPHRIN receptors play important role in establishing neural topography
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Diffusible molecules
Those molecules are secreted by target tissues.
They diffuse into extracellular fluids.
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Diffusible molecules
• They affect growth and survival of neurons and their processes.
• TROPIC diffusible molecules guide growing axons toward or away from source.
• Tropic molecules can be chemo-attractant and chemo-repellant molecules.
• TROPHIC diffusible molecules promote survival and growth of neurons and their processes.
• In the peripheral nervous system trophic molecules match axonal innervation with target tissue.
• Production of trophic molecules is activity dependent.
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Diffusible molecules can be
TROPIC: P like PATHWAY, guidance of growing axons towards or away from source.
TROPHIC: H like HEALTH, nourishment, survival and growth of neurons and their processes.
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CHEMOATTRACTION CHEMOREPULSION
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Tropic diffusible molecules
Chemo-attractanttropic molecules
Chemo-reppelanttropic molecules
Tropic diffusible molecules
NETRIN/SLIT family (netrin is chemo-attractant, slit antagonises netrin)
SEMAPHORINS (chemo-repellants)
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Trophic molecules (neurotrophins) and neurotrophin hypothesis
NEUROTROPHIN HYPOTHESIS: in development, the survival of neurons and their axonal connections
depends upon the availability of some minimal quantity of trophic factor.
Target tissues synthesize and secrete a limited quantity of trophic factor.
Survival of neuron and their specific connections depens upon successful competition among inputs for a
limited quantity of trophic factor.
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Neurotrophins
In maturity, regulated secretion of trophic factors may help shape neuronal
connections in response to injury or adaptation to new patterns of neural activity.
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Neurotrophins
NERVE GROWTH FACTOR (NGF)
BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF)
NT-4/5, NT-3
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Neurotrophins
• Neurotrophin receptors are TIROSINE KINASE RECEPTORS (TRK).
Results of TRK receptors can be:
• cell survival
• neurite outgrowth and neuronal differentiation
• activity-dependent plasticity
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Neurotrophin receptor p75
p75
RhoA
Neurite growth
C-Jun
Cell death
NF-kB
Cell survival
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Second messengers
Outcome