Role of semaphorin III in the developing rodent trigeminal system

Semaphorins are a large family of secreted and transmembrane glycoproteins. Sema ill, a member of the Class III semaphorins is a potent chemorepulsive signal for subsets of sensory axons and steers them away from tissue regio ns with high levels of expression. Previous studies in mutant mice lacking sema III gene showed various neural and nonneural abnormalities. In this st udy, we focused on the developing trigeminal pathway of sema III knockout m ice. We show that the peripheral and central trigeminal projections are imp aired during initial pathway formation when they develop into distinct nerv es or tracts. These axons defasciculate and compromise the normal bundling of nerves and restricted alignment of the central tract. In contrast to tri geminal projections, thalamocortical projections to the barrel cortex appea r normal. Furthermore, sema III receptor, neuropilin, is expressed during a short period of development when the tract is laid down, but not in the de veloping thalamocortical pathway. Peripherally, trigeminal axons express ne uropilin for longer duration than their central counterparts. In spite of p rojection errors, whisker follicle innervation appears normal and whisker-r elated patterns form in the trigeminal nuclei and upstream thalamic and cor tical centers. Our observations suggest that sema III plays a limited role during restriction of developing trigeminal axons to proper pathways and tr acts. Other molecular and cellular mechanisms must act in concert with sema phorins in ensuring target recognition, topographic order of projections, a nd patterning of neural connections.