EphA4 (Sek1) receptor tyrosine kinase is required for the development of the corticospinal tract

EphA4 (Sek1) receptor tyrosine kinase is required for the development of the corticospinal tract

^*Queensland Institute for Medical Research, Royal Brisbane Hospital, Herston, Queensland 4029, Australia; ^†Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria 3050, Australia; ^‡School of Physiotherapy and ^¶Department of Anatomy and Cell Biology, University of Melbourne, Victoria 3020, Australia; and ^§School of Psychology, University of New South Wales, New South Wales 2052, Australia

Communicated by Gustav J. V. Nossal, University of Melbourne, Parkville, Australia (received for review February 27, 1998)

Abstract

Members of the Eph family of tyrosine kinase receptors have been implicated in the regulation of developmental processes and, in particular, axon guidance in the developing nervous system. The function of the EphA4 (Sek1) receptor was explored through creation of a null mutant mouse. Mice with a null mutation in the EphA4 gene are viable and fertile but have a gross motor dysfunction, which is evidenced by a loss of coordination of limb movement and a resultant hopping, kangaroo-like gait. Consistent with the observed phenotype, anatomical studies and anterograde tracing experiments reveal major disruptions of the corticospinal tract within the medulla and spinal cord in the null mutant animals. These results demonstrate a critical role for EphA4 in establishing the corticospinal projection.

Footnotes

↵ ‖ To whom reprint requests should be addressed at: Queensland Institute of Medical Research, The Bancroft Centre, PO Royal Brisbane Hospital, Herston, Queensland 4029, Australia. e-mail: andrewBo{at}qimr.edu.au.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. 65138).
ABBREVIATIONS:

AC,

anterior commissure;

CST,

corticospinal tract;

kb,

kilobase;

E,

embryonic day