We have cloned a novel cDNA encoding a putative transmembrane protein, neur
estin, from the rat olfactory bulb. Neurestin was identified based on a seq
uence similar to that of the second extracellular loops of odorant receptor
s in the cysteine-rich CC box located immediately after EGF-like motifs. Ne
urestin shows homology to a neuregulin gene product, human gamma-heregulin,
a Drosophila receptor-type pair-rule gene product, Odd Oz (Odz) / Ten(m),
and Ten(a), suggesting a possible function in synapse formation and morphog
enesis. Recently, a mouse neurestin homolog has independently been cloned a
s DOC4 from the NIH-3T3 cell line. Northern blot analysis showed that neure
stin is highly expressed in the brain and also in other tissues at much low
er levels. In situ hybridization studies showed that neurestin is expressed
in many types of neurons, including pyramidal cells in the cerebral cortex
and tufted cells in the olfactory bulb during development. In adults, neur
estin is mainly expressed in olfactory and hippocampal granule cells, which
are known to be generated throughout adulthood. Nonetheless, in adults the
expression of neurestin was experimentally induced in external tufted cell
s during regeneration of olfactory sensory neurons. These results suggest a
role for neurestin in neuronal development and regeneration in the central
nervous system. (C) 1999 Academic Press.