GDNF-RELATED FACTOR PERSEPHIN IS WIDELY DISTRIBUTED THROUGHOUT THE NERVOUS-SYSTEM

Persephin (PSP) is the most recently discovered member of the GDNF fam ily of neurotrophic factors. We have used an RT-PCR approach to start addressing the putative functional significance of PSP by determining sites of its synthesis in the neonatal rat brain. Generally, two trans cripts were found. Sequence analysis of the transcripts identifies an 88 bp intronic sequence. Neural tissues analysed included cortex, hipp ocampus, striatum, diencephalon, mesencephalon, cerebellum, hindbrain and spinal cord as well as superior cervical, dorsal root ganglia, adr enal gland, and PC12 pheochromocytoma cells. As non-neuronal tissues, sciatic nerve, optic nerve, primary astroglial, oligodendroglial, O2A progenitor, and glioma cells (C6, B49) were also included. All tissues /cells except oligodendrocytes and O2A progenitor cells were strongly positive for PSP mRNA. To test the hypothesis of whether PSP might act as a target-derived factor, as suggested for GDNF, the motoneuron-mus cle axis has been analysed. PSP is synthesized in skeletal muscle and, to a higher extent, in the spinal cord. Moreover, PSP is synthesized in purified embryonic motoneurons. Together, these data do not support a role for PSP as a typical target-derived neurotrophic factor for mo toneurons. We conclude that PSP is synthesized throughout the nervous system and that it is presumably of both astroglial and neuronal origi n, in contrast to GDNF and neurturin, which seem to be predominantly o f neuronal origin. (C) 1998 Wiley-Liss, Inc.