Segregation of the receptor EphA7 from its tyrosine kinase-negative isoform on neurons in adult mouse brain

The EphA7 gene encodes not only a typical receptor tyrosine kinase (TK +) b ut also an isoform lacking the tyrosine kinase domain (TK -). We have made antibodies to localise EphA7 TK + and TK - isoforms in mouse brain. The TK - isoform was not detectable prenatally, despite reported expression of the TK - mRNA in the embryo. However, both TK + and TK - isoforms showed strik ing distributions in adult brain, TK + receptor immunoreactivity was strong in neuropil throughout most of the telencephalon, probably on fine arboris ations from neurons which expressed EphA7 during development tin cerebral c ortex, hippocampus, and striatum). In contrast, TK - receptor immunoreactiv ity was conspicuous on cell bodies and proximal dendrites of a limited numb er of neuronal types, some of which carried EphA7 TK + receptor on their ax one. This suggests that the TK - receptor, acting as a dominant negative an tagonist, may ensure that the TK + receptor only responds to signals encoun tered by the growing extremities of axons or dendrites. (C) 1999 Elsevier S cience B.V. All rights reserved.