Key concepts:

Figure 1. A neuron and growth cone. The upper panel shows the basic morphology of an extending axon. The motile tip of the axon is the growth cone. The lower panel is an enlargement of the growth cone, illustrating the cytoskeletal architecture underlying its structure. It can be seen from this image that if the F actins were depolymerised, the membrane projections would no longer be supported and the filopodia would retract into the main body of the growth cone. The microtubules mainly support the core of the growth cone and provide axonal structure.

Figure 2. The amphibian visual system. (a) The eyes and brain of an amphibian, demonstrating the connection between one eye and the contralateral (opposite) tectum by way of the optic nerve. The crossover of the nerve occurs at the optic chiasm. (b) Connectivity maps between the neurons of the retina and their targets in the tectum. Each coloured quadrant of the ‘left eye’ will project to the corresponding coloured quadrant within the ‘right tectum’.

Figure 3. Labelled lines. Simplified depiction of the choices that growth cones must make among the available fascicles. Specifically, this diagram shows the sibling G and C neurons crossing the midline of the grasshopper nervous system, ignoring the ipsilateral pathways (not shown) and some of the contralateral paths for a specific tract. It also demonstrates that though these neurons are related and they choose the same tract, their growth cones do not elect to extend in the same direction.

Figure 4. Segmental pathfinding of mammalian commissural axons. The axon of a commissural axon makes at least two decisions within the depicted cross section of the spinal cord. Decision 1 is to grow towards the first intermediate target (the floor plate). Decision 2 is to leave the floor plate region on the other side of the midline and grow towards the contralateral longitudinal fasciculus. Additional pathfinding decisions may include fasciculating with the longitudinal fasciculus and turning anteriorly, leaving the fascicle in the appropriate regions and extending into the thalamus (the final target).

Figure 5. Guidance cue actions in models of connectivity. (a) Schematic illustration of the actin-based filopodia and lamellipodia in the periphery of the growth cone, which transitions into a central domain of microtubules. Guidance cues impart directional information to the growth cone, shown in (1). Substrate-bound inhibitory (2) and permissive cues (3) create corridors of selective attractive and inhibitory domains. Secreted repulsive (4) and attractive (5) cues create gradients in the extracellular environment that direct growth cones away (4) or towards (5) a source of the cue. (b) Ephrin and Eph gradients of expression on retinal axons and along the surface of the tectum set up a system of coordinates for the formation of a retinotopic map. (c) Pioneer axons express molecules which are permissive to one type of axon due to selective adhesion (+) and may repel other types through selective repulsion (–), as illustrated in part (a). Axons preferentially grow along fascicles to which they adhere. (d) Segmental pathfinding forming the spinothalamic tract is regulated by a series of guidance cues encountered by the growing commissural axons. The initial axon growing from the cell body is repelled by BMPs secreted from the roof plate (1), and attracted to the floor plate by gradients of netrin and Shh (2). Once they have crossed the floor plate, axons lose responsiveness to the attractive molecules and gain sensitivity to floor plate-derived slits and semaphorins that drive them out (3). As they exit the floor plate, axons must also be directed anteriorly. This is accomplished by an inhibitory gradient of Wnt from the posterior (4), and another Wnt molecule acting through a separate receptor complex, attracting from the anterior (5). Additional molecules are involved in guidance through the brainstem and for targeting within the thalamus.