Distribution of PLP zy YX and Po mRNA during Rat Peripheral Nerve Development zy XW BA PIERLUIGI BARON, MICHAEL SHY," HITOSHI HONDA, MARIA SESSA, GIANCARLO CONTI, MARIA LAURA FELTRI," DAVID PLEASURE, AND JOHN KAMHOLZ zyx JIH Children's Hospital and Department zyxw of Neurology University of Pennsylvania, and "Thomas Jefferson University Philadelphia, Pennsylvania Myelinating Schwann cells express a unique set of structural proteins that inc the integral membrane protein Po, the major protein of peripheral nervous sy (PNS) myelin. They also express proteolipid protein (PLP), the major structu protein of central nervous system (CNS) myelin, although PLP is not inc rated in the PNS myelin sheath.' Schwann cell expression of Po and PLP genes apparently depends on neuronal signals and is inducible by CAMP.^^^ We have investigated transcription of Po and PLP during development of rat PNS by both in z F sifu hybridization and Northern blotting. In situ hybridizations were performed on frozen sections of nerve roots an sciatic nerve from rats zyxwv IHGFE 1, 10, and 40 days postnatal using uniformly labeled sens and antisense single-stranded RNA probes. The cRNA probes were transcrib from a 1.9-kb Po cDNA and a 1.4-kb PLP cDNA isolated from a rat sciatic nerve cDNA 1ibra1-y.~ Northern blotting was used to examine Po and PLP mRNA levels in proximal and distal segments of sciatic nerve from rats 5, 10, 30, and 40 days postnatal. PLP and Po mRNA were detected in nerve roots and sciatic nerves at all ag studied. PLP mRNA was distributed in clusters within the CNS in a pattern similar to that observed for Po in the PNS. PLP mRNA in the PNS, however, was more diffusely distributed. Grain density within the endoneurium for both PO and PLP was highest on postnatal day 10, which is consistent with Northern blot estimates of Po and PLP mRNA abundance in rat sciatic nerve. Neither PO nor PLP messages displayed a proximal-distal gradient during sciatic nerve develop- ment as judged by both in situ hybridization and Northern blotting. Our results demonstrate that Po and PLP mRNAs have a similar developmen- tal profile, although the relative increase in PLP transcription between days 1 10 is considerably less than that for Po. Both Po and PLP messages are also modulated uniformly along the nerve throughout development. These obs tions suggest that signals regulating Po and PLP transcription are expressed uni- formly along the nerve and do not display a proximal-distal gradient. We also that PLP message is distributed diffusely throughout the endoneurium, unlike message which is found in clusters around Schwann cell nuclei. This differenc 375