SELECTIVE COEXPRESSION OF INSULIN RECEPTOR-RELATED RECEPTOR (IRR) ANDTRK IN NGF-SENSITIVE NEURONS

The insulin receptor-related receptor (IRR) has recently been identifi ed as a member of the insulin receptor tyrosine kinase family; however , its endogenous ligand and biological function are still unknown. In contrast to the very widespread pattern of expression of the homologou s insulin and IGF-I receptors, IRR demonstrates a very restricted cell ular distribution. Using in situ hybridization and immunohistochemistr y, we now show that the expression of this receptor is selectively con centrated in a subset of neurons where its appearance is closely assoc iated with that of the NGF receptor TRK. IRR and TRK demonstrate synch ronized patterns of coexpression in neural crest-derived sensory and s ympathetic neurons and in non-neural crest basal forebrain and striata l neurons. Both appear early in the embryonic development of dorsal ro ot and trigeminal neurons and somewhat later, near the time of birth, in sympathetic neurons. Expression of both IRR and TRK appears perinat ally in basal forebrain neurons, reaching maximal levels about postnat al day 20. This association is highly selective, since TRK mRNA is not detected anywhere in the developing nervous system in the absence of coordinate IRR expression, and the same is true for inn expression wit h respect to TRK. In the adult rat, the majority of TRK-positive senso ry neurons still express IRR mRNA, and coexpression in sympathetic and forebrain neurons continues without evidence of diminution. These fin dings are consistent with a functional linkage of the IRR and TRK rece ptors in NGF-sensitive neurons.