RESCUE OF SENSORY GANGLIA THAT ARE PROGRAMMED TO DEGENERATE IN NORMALDEVELOPMENT - EVIDENCE THAT NGF MODULATES PROLIFERATION OF DRG CELLS IN-VIVO

The dorsal root ganglia (DRG, spinal ganglia) are a metameric series o f structures that develop from neural crest cells within the dorsal se mitic mesoderm. A striking element of patterning within this meristic series is the disappearance of the five or six most rostral DRG early in the embryonic development of birds and mammals. The transient DRG h ave been named ''Froriep's ganglia'' after their 19th century discover er (reviewed in Lim et al., 1987). The ontogeny of the longest survivi ng Froriep's ganglion of the chick embryo, DRG C2, has recently been e xamined in detail (Rosen er al., 1996). At St. 18 (Embryonic Day (E)2. 5+), the C2 DRG had the same shape and volume as permanent ganglia C5 and C6. C2's development first diverged from that of normal DRG at St. 19 (E3-), when C2 was observed to be half the size and shaped differe ntly from its neighbors, and its peripheral nerve root began to degene rate. Both lower proliferation and higher apoptosis rates contribute t o the reduced size of C2 compared to normal DRG at St. 19-20. One-thir d fewer C2 cells were found to be in S-phase when compared to neighbor ing ganglia, and apoptotic cells were more than three times more abund ant in C2 than in conventional DRG at this stage. Since growth factors modulate both proliferation and apoptosis, we postulated that these m olecules and/or their receptors might be responsible for the differenc e in fate between C2 and C5. In order to begin to evaluate this hypoth esis, we have now treated embryos with nerve growth factor (NGF) in ov o. NGF treatments partially rescued C2, producing a 50% reduction in t he normal difference in size between C2 and C5 at St. 23. At least par t of this rescue could be accounted for by increased levels of prolife ration in the NGF-treated C2 compared to those in control embryos. Pro liferation in normal DRG C5 was unaffected by NGF application. NGF tre atment rescued DRG cells in both C2 and C5 from cell death. Staining o f pycnotic nuclei revealed that NGF dramatically reduced the death in the C2 ganglia. In addition to providing insight into the early patter ning of the DRG, our results shed new light on the best-studied neurot rophic factor, NGF. Our finding is the first direct evidence for a rol e for NGF in control of DRG cell proliferation in vivo. (C) 1996 Acade mic Press, Inc.