Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formation

Donata Orioli, Mark Henkemeyer, Greg Lemke, Rüdiger Klein, Tony Pawson

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


Sek4 and Nuk are members of the Eph-related family of receptor protein-tyrosine kinases. These receptors interact with a set of cell surface ligands that have recently been implicated in axon guidance and fasciculation. We now demonstrate that the formation of the corpus callosum and anterior commissure, two major commissural axon tracts that connect the two cerebral hemispheres, is critically dependent on Sek4 and Nuk. While mice deficient in Nuk exhibit defects in pathfinding of anterior commissure axons, sek4 mutants have defects in corpus callosum formation. The phenotype in both axon tracts is markedly more severe in sek4/nuk1 double mutants, indicating that the two receptors act in a partially redundant fashion, sek4/nuk1 double mutants also exhibit specific guidance and fasciculation defects of diencephalic axon tracts. Moreover, while mice singly deficient in either Sek4 or Nuk are viable, most sek4/nuk1 double mutants die immediately after birth primarily due to a cleft palate. These results demonstrate essential and cooperative functions for Sek4 and Nuk in establishing axon pathways in the developing brain, and during the development of facial structures.

Original languageEnglish (US)
Pages (from-to)6035-6049
Number of pages15
JournalEMBO Journal
Issue number22
StatePublished - Nov 15 1996


  • Axon fasciculation
  • Axon guidance
  • Eph-related receptors
  • Palate formation
  • Tyrosine kinase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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