Neuronal network formation in the developing
nervous system is dependent on the accurate
navigation of nerve cell axons and dendrites,
which is controlled by attractive and repulsive
guidance cues. Ephrins and their cognate Eph
receptors mediate many repulsive axonal guidance
decisions by intercellular interactions
resulting in growth cone collapse and axon
retraction of the Eph-presenting neuron. We
show that the Rac-specific GTPase-activating
protein a2-chimaerin binds activated EphA4
and mediates EphA4-triggered axonal growth
cone collapse. a-Chimaerin mutant mice
display a phenotype similar to that of EphA4
mutant mice, including aberrant midline axon
guidance and defective spinal cord central pattern
generator activity. Our results reveal an achimaerin-dependent
signaling pathway downstream
of EphA4, which is essential for axon
guidance decisions and neuronal circuit formation
in vivo.