Functional analysis of zebrafish GDNF

We have identified zebrafish orthologues of glial cell line-derived neurotr ophic factor (GDNF) and the ligand-binding component of its receptor GFR al pha1. We examined the mRNA expression pattern of these genes in the develop ing spinal cord primary motor neurons (PMN), kidney, and enteric nervous sy stems (ENS) and have identified areas of correlated expression of the ligan d and the receptor that suggest functional significance. Many aspects of ze brafish GDNF expression appear conserved with those reported in mouse, rat, and avian systems. In the zebrafish PMN, GFR alpha1 is only expressed in t he Cap motor neuron while GDNF is expressed in the ventral semitic muscle t hat it innervates. To test the functional significance of this correlated e xpression pattern, we ectopically overexpressed GDNF in semitic muscle duri ng the period of motor axon outgrowth and found specific perturbations in t he pattern of CaP axon growth. We also depleted GDNF protein in zebrafish e mbryos using morpholino antisense oligos and found that GDNF protein is cri tical for the development of the zebrafish ENS but appears dispensable for the development of the kidney and PMN. (C) 2001 Academic Press.