EPHA4 (SEK1) RECEPTOR TYROSINE KINASE IS REQUIRED FOR THE DEVELOPMENTOF THE CORTICOSPINAL TRACT

Members of the Eph family of tyrosine kinase receptors have been impli cated in the regulation of developmental processes and, in particular, axon guidance in the developing nervous system. The function of the E phA4 (Sek1) receptor was explored through creation of a null mutant mo use. Mice with a null mutation in the EphA4 gene are viable and fertil e but have a gross motor dysfunction, which is evidenced by a loss of coordination of limb movement and a resultant hopping, kangaroo-like g ait. Consistent with the observed phenotype, anatomical studies and an terograde tracing experiments reveal major disruptions of the corticos pinal tract within the medulla and spinal cord in the null mutant anim als. These results demonstrate a critical role for EphA4 in establishi ng the corticospinal projection.