A fundamental feature of the developing nervous system is the ability of neurons to extend axons and navigate to appropriate synaptic targets. This activity is thought to depend on the ability of axons to interpret a variety of guidance signals, with a great deal of attention placed on secreted, long-range signals that act to attact or repel axonal growth. One of the most famous examples of a chemotropic guidance signal is the molecule netrin1. Netrin1 is prominently produced by floor plate cells in the ventral midline of the developing nervous and has been proposed to attract the growth of axons toward the floor plate. Work published today from our UCLA colleague Dr. Samantha Butler's lab and us shows that this model is inaccurate.
In addition to the floor plate, netrin1 is produced by neural progenitors and deposited on lateral pial surface, where it acts locally to promote axon growth and fasiculation (bundling). Deletion of the progenitor sources of netrin1 leads to profound axon guidance defects. By contrast, deletion of the netrin1 gene from the ventral midline or ablation of the formation of midline cells altogether does not greatly affect the ventrally directed growth of axons in the spinal cord. These findings together reveal that 1) neural progenitors are a major source of axon guidance cues for axons, and 2) netrin1 primarily functions in a short- and not long-range manner as previously suggested.