CELLULAR EXPRESSION OF GDNF MESSENGER-RNA SUGGESTS MULTIPLE FUNCTIONSINSIDE AND OUTSIDE THE NERVOUS-SYSTEM

Glial-cell-line-derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor-beta family and has potent neurotro phic effects on several classes of neurons including dopamine neurons and motoneurons. Here, we have used in situ hybridization to describe the development of the cellular expression of GDNF mRNA pre- and postn atally. Consistent with dopaminotrophic activity, GDNF mRNA is express ed in the developing basal ganglia and the olfactory tubercle. It is a lso found in a thalamic nucleus, in neurons of the substantia innomina ta, in the developing Purkinje neurons and the developing locus coerul eus area, and in trigeminal brainstem nuclei. In the spinal cord, neur onal expression is found in Clarke's column. GDNF mRNA is also express ed in the dorsal horns during development. Additional GDNF mRNA expres sion in the head region includes the carotid body, the retina, the vib rissae, the inner ear, the ear canal, and epithelium in the nasal cavi ty. Prominent expression is also found in the developing teeth. The wi despread expression of GDNF in developing skeletal muscle is consisten t with trophic activity on a-motoneurons. The smooth muscle layers of the gastrointestinal tract are also strongly positive. A very strong s ignal is found in the outer mesenchyme of the developing metanephric k idney. We conclude that GDNF mRNA is expressed in many different cellu lar systems inside and outside the central nervous system during devel opment, suggesting multiple functions of GDNF in the developing organi sm.