Role of EphA4 in defining the position of a motoneuron pool within the spinal cord

The correct assembly of the neural circuits that control movement requires the development of topographically organized pools of motoneurons within the spinal cord. The generation of a diverse array of motoneuron subtypes, which express differing transcription factors and cell-surface receptors, allows different motoneuron pools to be segregated to specific positions during development. In this investigation, we show that the Eph receptor tyrosine kinase, EphA4, appears to be important for the correct localization of a motoneuron pool to a specific position in the spinal cord. In the spinal cord of mice deficient in EphA4, the motoneuron pool that innervates the tibialis anterior muscle of the hindlimb is caudally displaced by approximately one vertebral segment. However, despite the abnormal position of the tibialis anterior motoneuron pool in the spinal cord of EphA4-deficient animals, the motoneurons of this pool still project to the tibialis anterior muscle of the hindlimb correctly. Additional analyses of other limb innervating motoneuron pools in the cervical and lumbar enlargements of the spinal cord of EphA4-deficient animals revealed them to be located in the appropriate segmental positions. Furthermore, we show that EphA4 does not appear to be important for spinal motoneuron survival as stereological quantification of the number of motoneurons present in the sciatic motoneuron pool of EphA4-deficient animals demonstrated these motoneurons to be present in the correct numbers. These observations suggest an important role for EphA4 in regulating the position of a specific motoneuron pool within the spinal cord.