The segmental arrangement of spinal nerves in higher vertebrate embryo
s provides a simple system in which to study the factors that influenc
e axon pathfinding. Developing motor and sensory axons are intimately
associated with surrounding tissues that direct axon guidance. We argu
e that two distinct guidance mechanisms, viz. contact repulsion and ch
emorepulsion, act simultaneously to prescribe spinal axon trajectories
by 'surround-repulsion'. Motor and sensory axons grow freely within t
he anterior half of each mesodermal somite, because they are excluded
from posterior half-somites by contact repulsion. By contrast, the dor
soventral trajectory that bipolar sensory axons of the dorsal root gan
glia follow is governed by diffusible repellents originating from the
notochord medially and dermamyotome laterally. Even though spinal nerv
e development appears to be a simple system for elucidating axon guida
nce mechanisms, many distinct candidate guidance molecules have been i
mplicated and their relative contributions remain to be evaluated.