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

Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13248-53. doi: 10.1073/pnas.95.22.13248.

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.

MeSH terms

  • Animals
  • Base Sequence
  • Fetal Proteins / genetics*
  • Fetal Proteins / physiology*
  • Gait
  • Gene Expression Regulation, Developmental*
  • Genotype
  • Homozygote
  • Medulla Oblongata / embryology*
  • Medulla Oblongata / physiopathology
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Movement Disorders / enzymology
  • Movement Disorders / genetics*
  • Nerve Fibers / pathology
  • Nerve Fibers / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Pathways / embryology
  • Neural Pathways / physiopathology
  • Polymerase Chain Reaction
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptor, EphA4
  • Recombination, Genetic
  • Restriction Mapping
  • Spinal Cord / embryology*
  • Spinal Cord / physiopathology
  • Stem Cells

Substances

  • Fetal Proteins
  • Nerve Tissue Proteins
  • Receptor Protein-Tyrosine Kinases
  • Receptor, EphA4

Associated data

  • GENBANK/UNKNOWN