THE DEVELOPMENTAL EXPRESSION IN THE RAT CNS AND PERIPHERAL-TISSUES OFPROTEASES PC5 AND PACE4 MESSENGER-RNAS - COMPARISON WITH OTHER PROPROTEIN PROCESSING ENZYMES

Many peptides modulating cellular growth and differentiation in develo pment are first synthesized as precursors that require proteolytic pro cessing by the ''prohormone convertase'' (PC) family of endoproteases. Using in situ hybridization, we have here determined that two recentl y identified PC members, PC5 and PACE4, are expressed prenatally in sp atial and temporal patterns that are each unique and distinct from tho se of previously characterized PCs. PC5 mRNA is first detected at e9 i n highly restricted regions of the neural tube, in caudal myotomes, an d at the materno-embryonic junction of the uterus. At e10, restricted PC5 mRNA expression is detected in the optic and otic vesicles, the ro of of midbrain, and trunk myotomes. By midgestation (e13-e16), PC5 mRN A expression in the developing nervous system has expanded to multiple regions including hippocampus, thalamus, hypothalamus, brain stem, an d spinal cord. By midgestational stages, PACE4 mRNA is expressed in mu ltiple regions of the developing nervous system, generally distinct fr om PC5, and including a uniquely high level of expression in the ventr icular zone of the hippocampus. In several peripheral organ systems, i ncluding lung and gut, we observed remarkably complementary patterns o f PC5 and PACE4 expression. In addition, PACE4 transcripts are express ed in the heart and liver, whereas PC5 is expressed in the adrenal and kidney primordia. These results suggest that both PC5 and PACE4 may b e involved in neuropeptide precursor processing in the developing nerv ous system and peripheral tissues with the general nonoverlapping expr ession patterns suggesting that PC5 and PACE4 may process distinct set s of proprotein substrates. (C) 1997 Academic Press.