Axonal Guidance and neurotropic factors

its a brief presentation on the topic of axonal guidance and neurotropic factors all the basis knowledge of the structure of growth cone formation and all the neurotropic factors

1. SGT UNIVERSITY Gurugram Subject – Advanced Neurobiochemistry And Immunology Topic – Axonal Guidance and Neurotropic Factors Presented by Ritu and Reetika MNNT III Sem FAHS, SGT University Submitted to Dr.Shweta Tripathi Assistant Professor FAHS, SGT University

2. Pre- Assessment

3. Q1. How do neurotrophic factors contribute to the development of the nervous system? A. By promoting neuron survival and eliminating those with unsuccessful axonal

connections

B. By inhibiting the growth and differentiation of axons

C. By preventing the formation of synapses

D. By reducing neuronal plasticity Q2. What is the primary mechanism by which axons are guided to their targets during nervous system development?

A. Chemoattraction B. Contact guidance

C. Chemorepulsion D. Growth cone dynamics

4. Q3. What is the primary role of chemoattraction in axon guidance? A. Repelling axons from specific chemical signals

B. Guiding axons towards specific chemical signals

C. Defining specific pathways for axon growth

D. Recognizing specific signals on target cells Q4. How do axons recognize their final destination in target recognition? A. By adhering to specific pathways defined by the extracellular matrix

B. By following specific chemical signals released by target cells

C. By repelling from specific chemical signals

D. By recognizing specific signals on target cells

5. Axonal Guidance and Neurotropic Factors Axonal guidance is the intricate process by which growing axons navigate the developing nervous system to reach their correct target cells. This journey is guided by a complex interplay of molecular cues and cellular interactions. Neuronal growth factors play a crucial role in supporting axon growth and survival during this journey.

6. Role of Neuronal Growth Factors Neuronal growth factors are proteins that promote the survival, growth, and differentiation of neurons. These essential molecules act as guiding signals, influencing axon elongation, branching, and target selection. 1 Promoting Survival Growth factors act as life-sustaining signals, preventing neurons from undergoing apoptosis (programmed cell death). 2 Stimulating Growth They trigger the production of proteins and other molecules necessary for axon elongation and branching. 3 Guiding Pathfinding Growth factors influence the direction of axon growth, ensuring they reach their appropriate targets.

7. Molecular Mechanisms of Axon Guidance Axon guidance is a complex process involving intricate molecular interactions. Guidance cues, such as chemoattractants and chemorepellents, bind to specific receptors on the axonal surface, triggering intracellular signaling cascades that influence axon behavior. 1 Signal Reception Guidance cues bind to receptors on the axonal surface, initiating a signaling cascade. 2 Signal Transduction The signal is relayed through a series of intracellular molecules, activating downstream effector proteins. 3 Growth Cone Response The signal alters the cytoskeleton and growth cone dynamics, directing axon growth towards or away from the cue.

8. Axon Development and Growth Cone Formation 1 Axon Initiation Axon development begins with the formation of a growth cone, a specialized structure at the tip of the axon. 2 Growth Cone Morphology The growth cone is characterized by filopodia and lamellipodia, which serve as exploratory structures that sense the environment. 3 Axon Extension The growth cone is highly dynamic and constantly extends, retracts, and turns as it navigates the environment towards its target.

9. Growth Cone Structure and Function Growth cones, the dynamic tips of axons, are responsible for sensing and responding to guidance cues. They have a complex structure, consisting of filopodia and lamellipodia, which explore the environment and direct axon growth. Filopodia Slender, finger-like projections that extend from the growth cone, probing the environment for guidance cues. Lamellipodia A flattened, sheet-like structure that forms a wider area of contact with the extracellular matrix. Cytoskeleton A network of microtubules and actin filaments that provides structural support and facilitates growth cone movement.

10. The Role of the Cytoskeleton in Growth Cone Dynamics T he cytoskeleton of the growth cone, composed of microtubules and actin filaments, plays a crucial role in shaping the growth cone, driving its motility, and mediating its responses to guidance cues. 1 Microtubules Microtubules extend from the axon shaft into the central region, providing structural support and serving as tracks for intracellular transport. 2 Actin Filaments Actin filaments are highly dynamic and form a network in the lamellipodia and filopodia, driving their extension and retraction. 3 Growth Cone Extension Microtubule polymerization and actin filament assembly drive the extension of the growth cone, propelling it forward. 4 Growth Cone Retraction Microtubule depolymerization and actin filament disassembly contribute to the retraction of the growth cone, allowing it to change direction.

11. Molecular Signals in Axonal Guidance Attractive Signals These signals draw the growth cone towards its target, often guiding it along specific pathways. They act as 'pulling forces' that guide the axon in the right direction. Repulsive Signals These signals push the growth cone away from specific areas, preventing it from straying into inappropriate regions. They act as 'pushing forces' to steer the axon away from undesirable areas. Netrin A protein family that acts as both attractive and repulsive signals. It guides axons in the developing nervous system towards specific target cells, influencing their final destination.

12. Flowchart of Axonal Guidance 1 Growth Cone Formation The axon develops a growth cone at its tip, which is a dynamic structure responsible for sensing and responding to guidance cues. 2 Signal Reception The growth cone receives signals from its environment, including attractants and repellents, through receptors on its surface. 3 Cytoskeletal Rearrangement The signals trigger a cascade of events leading to the rearrangement of the cytoskeleton within the growth cone, directing its movement. 4 Axon Extension The growth cone extends the axon in the direction of attractive signals, guided by the dynamic cytoskeletal changes. 5 Target Recognition When the axon reaches its target cell, the growth cone recognizes specific signals indicating its final destination.

13. Axon Pathfinding and Target Selection Axon pathfinding involves a series of decisions as axons navigate the intricate pathways of the nervous system. This journey is guided by a combination of guidance cues, growth factors, and interactions with other cells. Initial Growth Axons extend from the cell body, exploring the surrounding environment. Guidance Cue Interactions Axons respond to guidance cues, directing their growth towards or away from specific targets. Target Recognition Axons recognize their specific targets and establish connections, forming synapses.

14. Attractive and Repulsive Guidance Cues Attractive cues attract axons towards their target cells, while repulsive cues guide axons away from inappropriate pathways. These cues act in a coordinated manner to ensure precise axonal navigation. Attractive Cues These cues act like magnets, drawing axons towards their targets, promoting proper connections. Repulsive Cues These cues act like barriers, pushing axons away from inappropriate pathways, preventing misconnections .

15. Chemoattractant and Chemorepellent Signals Chemoattractants These molecules attract axons, promoting their growth towards specific target cells. Examples include netrins, Slit2, and BDNF. Chemorepellents These molecules repel axons, preventing them from growing in incorrect directions. Examples include semaphorins, ephrins, and Slit1. Gradient Formation Chemoattractants and chemorepellents are often expressed in gradients, allowing axons to sense direction and navigate towards or away from specific targets.

16. Guidance Cue Gradients Concentration Gradients Axon growth cones respond to differences in concentration of guidance cues, moving towards higher concentrations of attractants and away from higher concentrations of repellents. Directional Growth Guidance cue gradients establish a directional signal that guides the growth cone, ensuring that axons grow in the correct direction towards their targets.

17. Role of Extracellular Matrix in Axonal Guidance The extracellular matrix (ECM) is a complex network of molecules that surrounds cells and provides structural support and guidance cues. The ECM plays a significant role in guiding axons to their target cells. Laminin Laminin is a major component of the ECM that promotes axon growth and guidance. Collagen Collagen provides structural support and can influence axon directionality. Hyaluronan Hyaluronan is a glycosaminoglycan that regulates axon growth and migration.

18. Guidance Cues and their Receptors in Axonal Pathfinding Axonal guidance is achieved through a complex interplay between guidance cues, secreted or membrane-bound molecules that influence growth cone behavior, and their receptors, which detect and transduce signals. Guidance Cue Receptor Function Netrin-1 DCC (Deleted in Colorectal Cancer) Attracts axons towards target cells Slit Robo (Roundabout ) Repels axons from inappropriate pathways Semaphorin 3A Plexin-A1 Repels axons from inappropriate pathways

19. Ephrins and Eph Receptors in Axon Guidance Eph Receptors These are transmembrane receptor tyrosine kinases found on the surface of neurons. Ephrins These are membrane-bound ligands that bind to Eph receptors, triggering signaling pathways. Repulsive Guidance Ephrin-Eph receptor interactions typically lead to repulsive guidance of axons, preventing them from crossing certain boundaries. Fine-Tuning Ephrin-Eph interactions can also contribute to the fine-tuning of axonal projections within specific target areas.

20. Semaphorins and Neuropilins in Axon Guidance Semaphorins Neuropilins Function A family of secreted and membrane-bound proteins. Transmembrane receptors that bind to semaphorins. Mediate repulsive guidance of axons, ensuring correct pathfinding.

21. Netrins and Deleted in Colorectal Cancer (DCC) Receptors Netrins A family of secreted proteins that act as chemoattractants for axons. DCC Receptors Transmembrane receptors that bind to netrins, triggering signaling pathways that promote axonal growth. Axonal Growth Netrin-DCC interactions promote axonal growth and guidance towards specific targets. Synapse Formation Netrins also play a role in synapse formation, contributing to the establishment of functional neural circuits.

22. Slits and Robo Receptors in Axon Guidance Slits A family of secreted proteins that act as chemorepellents for axons. Robo Receptors Transmembrane receptors that bind to Slits, triggering signaling pathways that lead to axonal repulsion. Boundary Formation Slit-Robo interactions help to establish boundaries in the nervous system, guiding axons along specific pathways and preventing them from crossing into inappropriate areas.

23. Neurotropic Factors Definition and Importance 1 What Are They? Neurotrophic factors are a group of proteins that promote the survival, growth, and differentiation of neurons. 2 Why Are They Important? They play a critical role in the development, maintenance, and repair of the nervous system. 3 Their Impact Neurotrophic factors influence neuronal function, plasticity, and response to injury.

24. Neurotrophic Factors and their Receptors 1 Brain-Derived Neurotrophic Factor (BDNF) A powerful neurotrophic factor that supports the survival and growth of neurons, particularly in the hippocampus and cortex. 2 Nerve Growth Factor (NGF) A key neurotrophic factor for sensory and sympathetic neurons, promoting their survival, growth, and differentiation. 3 Neurotrophin-3 (NT-3) A neurotrophic factor that promotes the survival and differentiation of motor neurons and other neuronal populations. 4 Neurotrophin-4/5 (NT-4/5) A neurotrophic factor that is structurally similar to BDNF and plays a role in the development and function of various neuronal populations.

25. Role of Neurotrophic Factors in Axon Guidance 1 Survival Neurotrophic factors promote the survival of neurons, ensuring that only those with successful axonal connections are maintained. 2 Growth and Differentiation Neurotrophic factors stimulate the growth and differentiation of axons, enabling them to reach their correct targets. 3 Synapse Formation Neurotrophic factors contribute to the formation of synapses, strengthening the connections between neurons and establishing functional neural circuits. 4 Plasticity Neurotrophic factors play a role in neural plasticity, allowing for the adaptation and refinement of neuronal connections throughout life.

26. Mechanism of Neurotrophic Factor Signaling Receptor Binding Neurotrophic factors bind to specific receptors on the surface of target neurons. Signal Transduction This binding activates a signaling cascade within the neuron, leading to changes in gene expression. Transcriptional Activation These changes in gene expression promote the production of proteins that support survival, growth, and guidance of axons.

27. Nerve Growth Factor (NGF) Discovery NGF was the first neurotrophic factor to be discovered. It was isolated in the 1950s by Rita Levi-Montalcini and Stanley Cohen. Function NGF plays a crucial role in the development and maintenance of sensory and sympathetic neurons. It promotes the survival, growth, and differentiation of these neurons. Clinical Significance NGF has shown promise in treating various neurological disorders, including Alzheimer's disease and Parkinson's disease.

28. Brain-Derived Neurotrophic Factor (BDNF) Synaptic Plasticity BDNF enhances synaptic plasticity, the ability of synapses to strengthen or weaken over time. Learning and Memory BDNF plays a critical role in learning and memory formation. Neuroprotection BDNF protects neurons from damage and promotes their survival.

29. Ciliary Neurotrophic Factor (CNTF) Function Promotes survival and differentiation of motor neurons, retinal ganglion cells, and other neuronal populations. Clinical Applications Being explored for treatment of amyotrophic lateral sclerosis (ALS), retinal degeneration, and other neurological disorders. Potential Benefits Could improve motor function, protect neurons from degeneration, and promote nerve regeneration.

30. Glial Cell Line-Derived Neurotrophic Factor (GDNF) 1 Discovery GDNF was first discovered in 1993. 2 Function GDNF plays a critical role in the survival and differentiation of dopaminergic neurons, which are essential for movement control. 3 Clinical Applications GDNF is being investigated for the treatment of Parkinson's disease and other neurodegenerative disorders.

31. Axonal Guidance Disorders and Implications Disruptions in axonal guidance can lead to a range of developmental defects and neurological disorders. These disorders often result from mutations in genes involved in axonal guidance signaling pathways. 1 Spinal Muscular Atrophy A neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene, which is involved in axonal growth and maintenance. 2 Autism Spectrum Disorder A complex neurodevelopmental disorder characterized by impairments in social interaction and communication, which may involve alterations in axonal guidance. 3 Intellectual Disability A condition characterized by significant limitations in cognitive function, which can be caused by defects in axonal guidance and neuronal connectivity. 4 Cerebral Palsy A group of disorders affecting movement and coordination, which can be caused by damage to the brain during development, potentially affecting axonal guidance.

32. Implications in Nervous System Development Axonal guidance and neuronal growth factors are crucial for proper nervous system development. Disruptions in these processes can lead to neurological disorders, including autism, epilepsy, and Alzheimer's disease. Cognitive Development Proper axonal connections are essential for cognitive functions, such as learning and memory. Motor Control Accurate axonal guidance is crucial for coordinating muscle movement and maintaining balance. Sensory Perception Axon pathways convey sensory information from the body to the brain , enabling our senses to perceive the world.

33. Clinical Relevance and Future Directions Understanding axonal guidance and neuronal growth factors has important clinical implications. Research is ongoing to develop therapies for neurological disorders by promoting axonal regeneration and neuronal survival. Neurodegenerative Diseases Targeting growth factors could help slow or reverse neuronal loss in diseases like Alzheimer's and Parkinson's. Spinal Cord Injuries Enhancing growth factor activity might promote axonal regeneration and functional recovery after spinal cord injury. Stroke Growth factors could aid in neuronal survival and recovery after stroke, promoting brain function recovery.

34. Post- Assessment

35. Q1. What are Netrins and DCC Receptors in the context of axonal guidance? A. Transcription factors

B. Secreted proteins and transmembrane receptors

C. Neurotransmitters

D. Ion channels Q2. What is the role of the extracellular matrix in axonal guidance? A. Provides structural support and guidance cues

B. Attracts or repels axons

C. Facilitates communication between neurons and other cells

D. Produces glucose for energy

36. Q3. Which type of cells are supported by neurotrophic factors, such as NGF and BDNF? A. Astrocytes

B. Oligodendrocytes

C. Motor neurons, cortical neurons, hippocampal neurons

D. Microglia Q4. What is the initial stage of axonal guidance? A. Signal Reception

B. Cytoskeletal Rearrangement

C. Growth Cone Formation

D. Target Recognition

37. Q5. What do Semaphorins and Neuropilins regulate in axon guidance? A. Attraction of axons towards targets

B. Repulsion of axons away from targets

C. Growth of axons

D. Survival of neurons Q6. What are the finger-like projections present on the axon growth cones? A. Filopodia B. Lamellipodia C. Dendrites

D. Axons

38. Q7. Which structures in the growth cone are responsible for sensing the environment? A. Filopodia and lamellipodia B. Axon shaft C. Neuron cell body D. Myelin sheath Q8. Guidance cues, such as Netrins , Slits, and Semaphorins , each have a corresponding extit {______} on the axonal surface

A. Receptor

B. Enzyme

C. Neurotransmitter

D. Neurotrophic factor

39. Q9. Axons respond to guidance cues, directing their growth towards or away from specific targets. This process is known as extit {______} A. Axon degeneration B. Neuronal apoptosis C. Guidance cue interactions D. Axon pathfinding Q10. Chemoattractants are guidance cues that can act as both attractants and extit {______},
depending on the specific receptor involved

A. Activators

B. Inhibitors

C. Proteins

D. Nucleotides

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