Summary

1. Growth cones use lamellipodia and filopodia to move in an amoeba-like fashion, trailing the growing axon (or dendrite) behind them. The cell body sends building materials anterogradely to the growth cone, which sends retrograde signals back to the cell body. See Figures 5.1 and 5.2
2. Molecules of tubulin polymerize to add to the tip of the microtubule core of the axon, and they are polymerized or depolymerized within the growth cone as it responds to external cues. See Figures 5.3 and 5.4
3. An adhesive substrate is necessary for growth cone movement, but several families of signaling molecules direct growth cones through either short-range contact guidance or longer-range chemotropism. Both types of cues can be either attractive or repulsive. See Figure 5.5
4. Actin provides force to push filopodia forward and retract them again. If the filopodium adheres firmly enough to an external factor, contraction will pull the rest of the growth cone in that direction. External signals that cause the filopodium to collapse will turn the growth cone away. See Figure 5.6
5. Families of guidance cues and their receptors mediate contact guidance, including cell adhesion molecules like NCAM and L1 that bind to each other (by either heterophilic or homophilic binding), cadherins (homophilic binding), ephrins (heterophilic binding), and the integrins, which bind molecules in the extracellular matrix. See Figure 5.7
6. Families of chemotactic guidance cues include the netrins (binding unc-5 and Frazzled receptors), Slit (binding Robo), and semaphorins (binding plexin and neuropilin receptors). See Figure 5.8 and Table 5.1
7. The earliest axons from pioneer neurons may rely on guidepost cells and the other cues to establish a pathway that later axons may join by fasciculation. See Figures 5.9 and 5.10
8. Multiple studies indicate that there are general orientation cues for all three body axes available for growth cone navigation, such that they can orient, for instance, caudally in the dorsal lateral quadrant of the nervous system. See Figure 5.11
9. Axons of commissural neurons expressing Frazzled are attracted to netrin molecules in the midline, but after crossing the midline, they begin expressing Robo and are then repulsed by midline Slit and stop expressing Frazzled. Longitudinal axons express Robo from the start and so are repulsed by midline Slit, never crossing the midline. See Figures 5.12–5.15
10. Different groups of motor neurons express different transcription factors (as detailed in Chapter 4), and their axons navigate to reach the proper muscle targets. If transposed, motor neuronal axons can take novel pathways to reach their original targets, indicating there are long-range cues to guide them. See Figures 5.16 and 5.17
11. Amphibian and fish retinal ganglion cells can also take novel pathways to reach their appropriate targets in the tectum. Their growth cones are attracted to some contact guidance cues and repulsed by others. The concentration gradient of nasal-to-temporal retinal axons innervate the tectum in an anterior-to-posterior gradient, establishing a two-dimensional visual field on the tectum. See Figures 5.18–5.21
12. Cortical axons establishing the corpus callosum (CC) are attracted to the midline using the Robo-Slit signaling system, and are then deflected across the midline by a glial “bridge” to then innervate homologous portions of the contralateral cortex. All eutherian mammal species have a CC, but some people born without a CC (AgCC) show little or no behavioral deficits. On the other hand, fetal alcohol exposure, in addition to raising the risk of AgCC, often results in some degree of mental impairment.