Rescue of sensory ganglia that are programmed to degenerate in normal development: evidence that NGF modulates proliferation of DRG cells in vivo.

The dorsal root ganglia (DRG, spinal ganglia) are a metameric series of structures that develop from neural crest cells within the dorsal somitic 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 have been named "Froriep's ganglia" after their 19th century discoverer (reviewed in Lim et al., 1987). The ontogeny of the longest surviving Froriep's ganglion of the chick embryo, DRG C2, has recently been examined in detail (Rosen et 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 differently from its neighbors, and its peripheral nerve root began to degenerate. Both lower proliferation and higher apoptosis rates contribute to the reduced size of C2 compared to normal DRG at St. 19-20. One-third fewer C2 cells were found to be in S-phase when compared to neighboring ganglia, and apoptotic cells were more than three times more abundant in C2 than in conventional DRG at this stage. Since growth factors modulate both proliferation and apoptosis, we postulated that these molecules and/or their receptors might be responsible for the difference in fate between C2 and C5. In order to begin to evaluate this hypothesis, we have now treated embryos with nerve growth factor (NGF) in ovo. NGF treatments partially rescued C2, producing a 50% reduction in the normal difference in size between C2 and C5 at St. 23. At least part of this rescue could be accounted for by increased levels of proliferation in the NGF-treated C2 compared to those in control embryos. Proliferation in normal DRG C5 was unaffected by NGF application. NGF treatment rescued DRG cells in both C2 and C5 from cell death. Staining of pycnotic nuclei revealed that NGF dramatically reduced the death in the C2 ganglia. In addition to providing insight into the early patterning of the DRG, our results shed new light on the best-studied neurotrophic factor, NGF. Our finding is the first direct evidence for a role for NGF in control of DRG cell proliferation in vivo.