Early brain
development part two
DOMINA PETRIC, MD
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.
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
Growht
cone
https://cmgm.stanford.edu
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
Molecular signals for axon guidance
cell-associated
molecules
diffusible molecules
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
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.
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
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
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
Diffusible molecules
Those molecules are
secreted by target tissues.
They diffuse into
extracellular fluids.
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
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.
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
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.
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
CHEMOATTRACTION CHEMOREPULSION
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
Tropic diffusible molecules
Chemo-attractant
tropic molecules
Chemo-reppelant
tropic molecules
Tropic diffusible molecules
NETRIN/SLIT family (netrin is
chemo-attractant, slit antagonises
netrin)
SEMAPHORINS (chemo-repellants)
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
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.
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
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.
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
Neurotrophins
NERVE GROWTH FACTOR (NGF)
BRAIN DERIVED NEUROTROPHIC
FACTOR (BDNF)
NT-4/5, NT-3
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
Neurotrophins
• Neurotrophin receptors are TIROSINE
KINASE RECEPTORS (TRK).
Results of TRK receptors can be:
• cell survival
• neurite outgrowth and neuronal
differentiation
• activity-dependent plasticity
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
Neurotrophin receptor p75
p75
RhoA
Neurite
growth
C-Jun
Cell
death
NF-kB
Cell
survival
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
Second
messengers
Outcome
Literature
https://www.coursera.org/learn/medical-
neuroscience/lecture: Leonard E. White,
PhD, Duke University
https://cmgm.stanford.edu
HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY

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Early brain development part two

  • 1. Early brain development part two DOMINA PETRIC, MD
  • 2. 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. HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 4. Molecular signals for axon guidance cell-associated molecules diffusible molecules HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 5. 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. HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 6. 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 HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 7. Diffusible molecules Those molecules are secreted by target tissues. They diffuse into extracellular fluids. HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 8. 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. HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 9. 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. HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 10. CHEMOATTRACTION CHEMOREPULSION HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY Tropic diffusible molecules Chemo-attractant tropic molecules Chemo-reppelant tropic molecules
  • 11. Tropic diffusible molecules NETRIN/SLIT family (netrin is chemo-attractant, slit antagonises netrin) SEMAPHORINS (chemo-repellants) HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 12. 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. HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 13. 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. HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 14. Neurotrophins NERVE GROWTH FACTOR (NGF) BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF) NT-4/5, NT-3 HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 15. Neurotrophins • Neurotrophin receptors are TIROSINE KINASE RECEPTORS (TRK). Results of TRK receptors can be: • cell survival • neurite outgrowth and neuronal differentiation • activity-dependent plasticity HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY
  • 17. Literature https://www.coursera.org/learn/medical- neuroscience/lecture: Leonard E. White, PhD, Duke University https://cmgm.stanford.edu HTTPS://WWW.COURSERA.ORG/LEARN/MEDICAL-NEUROSCIENCE/LECTURE: LEONARD E. WHITE, PHD, DUKE UNIVERSITY