Frizzled3 controls axonal development in distinct populations of cranial and spinal motor neurons

Disruption of the Frizzled3 (Fz3) gene leads to defects in axonal growth in the VIIth and XIIth cranial motor nerves, the phrenic nerve, and the dorsal motor nerve in fore-and hindlimbs. In Fz3(-/-) limbs, dorsal axons stall at a precise location in the nerve plexus, and, in contrast to the phenotypes of several other axon path-finding mutants, Fz3(-/-) dorsal axons do not reroute to other trajectories. Affected motor neurons undergo cell death 2 days prior to the normal wave of developmental cell death that coincides with innervation of muscle targets, providing in vivo evidence for the idea that developing neurons with long-range axons are programmed to die unless their axons arrive at intermediate targets on schedule. These experiments implicate planar cell polarity (PCP) signaling in motor axon growth and they highlight the question of how PCP proteins, which form cell-cell complexes in epithelia, function in the dynamic context of axonal growth.