Morphogen signaling at the vertebrate growth cone: a few cases or a general strategy?

Axon navigation relies on the competence of growth cones to sense and interpret attractive and repulsive guidance cues present along their trajectory. For most neurons, this process is mediated by a limited number of conserved families of ligand-receptor signaling systems, including Ephrin/Eph, Netrins/DCC-Unc5, Slits/Robo, and Semaphorins/Plexin-Neuropilin. Recent studies have demonstrated that some neurons respond also to well-known secreted signaling molecules, best known for their roles as morphogens, such as BMP7, SHH, FGF8, and Wnt. Thus, retina ganglion cell axon navigation is influenced by FGF, SHH, and possibly BMP signaling. Similarly, commissural neurons in the spinal cord respond sequentially to the activity of BMP, SHH, and Wnt to extend toward and away from their intermediate target, the floor plate. The data that support this conclusion will be summarized and how morphogens may signal at the growth cone will be discussed.