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.
Leonard E. White, PhD, Duke University

3. Growht cone https://cmgm.stanford.edu
Leonard E. White, PhD, Duke University

4. Molecular signals for axon guidance
cell-associated molecules
diffusible molecules
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.
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
Leonard E. White, PhD, Duke University

7. Those molecules are secreted by target tissues.
Diffusible molecules
Those molecules are secreted by target tissues.
They diffuse into extracellular fluids.
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.
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.
Leonard E. White, PhD, Duke University

10. Tropic diffusible molecules
CHEMOATTRACTION
CHEMOREPULSION
Chemo-reppelant
tropic molecules
Chemo-attractant
tropic molecules
Axon
Axon
Axon
Axon
Leonard E. White, PhD, Duke University

11. Tropic diffusible molecules
NETRIN/SLIT family (netrin is chemo-attractant, slit antagonises netrin)
SEMAPHORINS (chemo-repellants)
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.
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.
Leonard E. White, PhD, Duke University

14. Neurotrophins NERVE GROWTH FACTOR (NGF)
BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF)
NT-4/5, NT-3
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
Leonard E. White, PhD, Duke University

16. Neurotrophin receptor p75
RhoA
Neurite growth
C-Jun
Cell death
NF-kB
Cell survival
Second
messengers
Outcome
Leonard E. White, PhD, Duke University

17. Literature
Leonard E. White, PhD, Duke University
Leonard E. White, PhD, Duke University