Mark Henkemeyer*, Donata Orioli#, Jeffrey T. Henderson!,Tracy M. Saxon*, John Roder!, Tony Pawson* and Rudiger Klein#

* Samuel Lunenfeld Research Institute, Mount Sinai Hospital,
* Program in Molecular Biology and Cancer, Program and Development and Fetal Health, 600 University Ave.,Toronto, Ontario M5G-1X5
# European Molecular Biology Laboratory, Meyerhosftrasse 1, D-69117,Heidelberg, Germany

Cell, 86, pp. 35-46, 1996

Abstract

Eph family receptor tyrosine kinases have been proposed to control axonguidance and fasciculation. To address the biological functions of theEph family member Nuk, two mutations in the mouse germ line have been generated:a protein null allele (Nuk1) and an allele that encodes a Nuk-Bgal fusionreceptor lacking the tyrosine kinase and C-terminal domains (Nuk-lacZ). In Nuk1 homozygotes, the majority of axons forming the posterior compoment of the anterior commissure migrate aberrantly to the floor of the brain, resulting in a failure of cortical neurons to link the opposing temporal lobes. These results indicate that Nuk, a receptor binding trans-membrane ligands plays a critical and unique role in the pathfinding of specificaxons in the mammalian central nervous system.