FOCAL EXPRESSION OF GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR IN DEVELOPING MOUSE LIMB BUD

Glial cell line-derived neurotrophic factor (GDNF) is known to support the survival of motoneurons in vitro and in vivo, as well as subpopul ations of sensory neurons in vitro. To clarify the mechanisms by which GDNF supports these neurons, we examined the patterns of GDNF mRNA ex pression in relation to motor and sensory axons during early stages of mouse development. Between embryonic days (E) 10 and 12, a time when motor and sensory axons are entering the periphery, GDNF mRNA is expre ssed at high levels in a restricted region in proximal limb buds where axons converge and enter the limb. At later ages (E14-16), GDNF mRNA was detected in non-neuronal cells along peripheral nerve, in dermis, and in some muscles. To characterize cells that express GDNF in the pr oximal limb, GDNF expression in the forelimb was compared to expressio n patterns of two markers of muscle, Pax 3 and myogenin, as well as wi th the pan neurotrophin receptor (p75) which is expressed by Schwann c ell precursors. We show that expression of GDNF in the proximal limb b ud at E11-12 does not correlate with markers of muscle or Schwann cell precursors, which supports the idea that GDNF is expressed by mesench ymal cells in this region. Our results suggest that GDNF expression in proximal limb buds may function as a transient survival factor, parti cularly for motor neurons, before they reach their final targets. GDNF expression in muscle and dermis at later stages suggests that GDNF ma y have additional functions as motor and sensory neurons mature.