NERVE GROWTH-FACTOR RECEPTOR TRKA IS DOWN-REGULATED DURING POSTNATAL-DEVELOPMENT BY A SUBSET OF DORSAL-ROOT GANGLION NEURONS

Nerve growth factor (NGF), signaling through its receptor tyrosine kin ase, TrkA, is required for the survival of all small and many intermed iate-sized murine dorsal root ganglion (DRG) neurons during developmen t, accounting for 80% of the total DRG population. Surprisingly, NGF/T rkA-dependent neurons include a large population that does not express TrkA in adult mice (Silos-Santiago et al., 1995). This finding sugges ts two hypotheses: Neurons lacking TrkA in the adult may express TrkA during development, or they may be maintained through a paracrine mech anism by TrkA-expressing neurons. To determine whether TrkA is express ed transiently by DRG neurons that lack the receptor in adulthood, we examined the distribution of TrkA protein during development. We show here that TrkA expression is strikingly developmentally regulated. Eig hty percent of DRG neurons expressed TrkA during embryogenesis and ear ly postnatal life, whereas only 43% expressed TrkA at postnatal day (P ) 21. Because the period of TrkA down-regulation corresponds with a cr itical period during which nociceptive phenotype can be altered by NGF (see Lewin and Mendell [1993] Trends Neurosci. 26:353-359), we examin ed whether NGF modulates the downregulation of TrkA. Surprisingly, nei ther NGF deprivation nor augmentation altered the extent of TrkA down- regulation. Our results demonstrate a novel form of regulation of neur otrophin receptor expression that occurs late in development. All DRG neurons that require NGF for survival express TrkA during embryogenesi s, and many continue to express TrkA during a postnatal period when ne uronal phenotype is regulated by NGF. The subsequent down-regulation o f TrkA is likely to be importantly related to functional distinctions among nociceptive neurons in maturity. (C) 1997 Wiley-Liss, Inc.