Spatiotemporal patterns of expression of NGF and the low-affinity NGF receptor in rat embryos suggest functional roles in tissue morphogenesis and myogenesis.

We show here that NGF and its low-affinity receptor (p75NGFR) are expressed during rat embryogenesis at sites that are known to have important roles in tissue morphogenesis and myogenesis. The developing skin of the maxilla, the mandible, and the limb showed very similar patterns of NGF and p75NGFR expression. However, NGF and p75NGFR expression in the developing limb initiated at the limb bud stage and was concentrated at proximal and distal developmental sites that have been reported to be involved in limb morphogenesis. Expression at the proximal/distal ends of the limb persisted throughout limb development, with some of the highest levels of expression occurring at the limb axillary sites, which were not highly innervated. We have also found p75NGFR expression at sites of mesenchymal/epithelial interactions in several developing organs that do not appear to have an adjacent source of NGF and may therefore be sites that bind and respond to the other members of the NGF family (brain-derived neurotrophic factor and neurotrophin-3). These organs include the lung, testes, and kidney, where expression of p75NGFR occurred during the morphogenesis of specific epithelial structures and was coexpressed with the cell adhesion molecule NCAM. In addition, we found that NGF and p75NGFR were expressed during myogenesis. p75NGFR was observed in myoblast cells expressing MyoD1, a myoblast differentiation marker, and NGF transcripts in cells just adjacent to the developing myoblasts. When the myoblasts differentiate into myotubes, p75NGFR and MyoD1 cease to be expressed and the adjacent cells concomitantly cease to be make NGF. However, NGF and p75NGFR were not present in the early muscle precursor cells of the myotome of the somites but were observed in the dermatome and sclerotome, respectively. These results suggest that NGF and p75NGFR have functional roles in developmental processes that affect morphogenesis and cell differentiation.