CDNA SEQUENCE AND DIFFERENTIAL MESSENGER-RNA REGULATION OF 2 FORMS OF GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR IN SCHWANN-CELLS AND RAT SKELETAL-MUSCLE

Total RNA from rat Schwann cells grown in culture and adult rat skeletal muscle was reverse transcribed, amplified for glial cell line-derived neurotrophic factor (GDNF) messenger RNA (mRNA) using the polymerase chain reaction (PCR), and the PCR products sequenced. Two forms of GDNF were detected in the PCR step, one of a predicted size (GDNF(633)) and a second smaller form missing a 78-base pair sequence (GDNF(555)). Sequence analysis demonstrated that GDNF(633) is similar to the published sequence of GDNF differing only at three nucleotides, Southern and Northern blot analyses reveal that the two forms are probably derived from a single RNA species that is alternatively spliced. Interestingly, GDNF(633) mRNA was found to be selectively upregulated in denervated rat skeletal muscle at 1-2 weeks following axotomy, providing evidence that the innervation status of the muscle may determine the expression profile of the two alternately spliced forms. Given these findings, we suggest that GDNF may function as a target-derived trophic factor for neuronal populations innervating skeletal muscle, including sensory neurons and spinal cord motoneurons. (C) 1995 Academic Press, Inc.