Slides notes 2/17

Complex processes of axon and dendrite development are vital for proper brain wiring.
Fig. 5.1: Visualization of neuron structures using different microscopy techniques.
- (A) Fly medulla reconstruction using transmission electron microscopy (TEM).
- (B) Brainbow technique: A genetic strategy enabling various colors for neuron visualization, showcasing the interconnection of axons and dendrites in the hippocampus.

Fig. 5.3: Illustration of hippocampal neuron differentiation in culture.
- Neurons initially extend multiple equal processes.
- One processes, the future axon, accelerates growth, collecting specific components.
- Dendrites later form from the remaining minor processes.
- Integration point: Neurons process signals through dendrites into the soma at the axon hillock, leading to the development of neuronal polarity influenced by environmental signals.

Fig. 5.5: Development of axon complexity in zebrafish.
- Analysis of increasing complexity over 20 hours in embryonic development, depicting the emergence of new axons.
Early connectivity is less complicated with the initial growth of axons and dendrites.

Fig. 5.6: Role of guidepost cells in axon guidance.
- (A) Grasshopper embryo shows leg development.
- (B) Ti1 pioneer axons move along pathways guided by blue guidepost neurons; ablation of guide cells leads to disruptions in axon navigation.
Fig. 5.7: Experimental confirmation of external cues in axonal guidance.
- Mauthner cells grow guided by local environmental cues indicating the significance of guidance molecules in axon navigation.

Fig. 5.8: Analogy of axon navigation to urban driving.
- Axons navigate using molecular cues on surfaces to determine trajectories and targets.
Fig. 5.12: Active growth cones in retinal axons.
- Even when severed, growth cones can navigate accurately, indicating intrinsic capabilities.

Historical Observations:
- Speidel (1941): Documented live growth cones on sensory axons in tadpoles.
- Ramón y Cajal (1890): Recorded axonal expansions during early embryonic development.
Fig. 5.13: Growth cone behavior and morphology differences between leading and following axons.
- Leader axons face complex cues and slower progression compared to faster-growing follower axons.

Fig. 5.12: Distinct roles of microtubules and actin in axonal structure and growth.
- Microtubules added at the growth cone tip confirm axonal extension dynamics.
Fig. 5.14: Structure of growth cones illustrates the arrangement of actin and microtubules.

Fig. 5.15: Actin filaments' involvement in guiding growth cones.
Fig. 5.18: Demonstrates how localized changes in the cytoskeleton can direct growth cone movement through depolymerization and stabilization of actin and microtubules.
Chemotactic navigation illustrated in Fig. 5.35 shows growth cone response to gradients of nerve growth factor (NGF) and Netrin, demonstrating molecular signaling’s role in axon direction.

Fig. 5.23: Shows how the adhesive properties of substrates affect growth cone behavior, with a tendency to prefer more adhesive trails.
Fig. 5.24: Key adhesion molecules on growth cones.
- Cadherins: Play a role in cell adhesion and are often homophilic.

Fig. 5.32: Examines the role of guidance molecules like Netrin and Slit in the correct neuronal pathway.
Fig. 5.41: Introduces the modulation of axonal turning through cAMP levels, affecting responses to Netrin.

Comprehensive understanding of axon navigation indicates the interplay of intrinsic neuronal properties and extrinsic environmental factors driving brain development, revealing critical insights into neural connectivity and potential implications for neuronal repair and regeneration.