Neurotrophins Cause a New Sensation

Abstract

positive neurons, loss of spinal projections from muscle afferents, and severe movement abnormalities. These features are consistent with the hypothesis that TrkC neurons convey proprioceptive information (Ernfors et An important organizational principle of the developing al., 1994b; Fariñ as et al., 1994; Klein et al., 1994). In peripheral nervous system is the reliance of neurons on the periphery, proprioceptive axons convey information specific members of the NGF family of neurotrophins from stretch and tension receptors (muscle spindles and for survival. The primary sensory neurons of the dorsal Golgi tendon organs) in skeletal muscle. NT-3 mRNA is root ganglion (DRG) have become a favored group for diffusely expressed in muscle during development but exploring neurotrophin function owing to both their acbecomes restricted to muscle spindles, a target end cessibility for in vivo and in vitro studies and the potential organ of proprioceptive afferents, postnatally (Schecterimportance of neurotrophins in regulating sensory funcson and Bothwell, 1992; Copray and Brouwer, 1994). tions, particularly pain. Neurotrophin studies have bene-The most puzzling groups of DRG neurons related to fited from the wealth of information available about the neurotrophin dependence have been the low threshold physiological properties, peptide expression, cytoskelecutaneous mechanoreceptive neurons that convey intal markers, and connectivity of DRG neurons (see Scott, formation from receptor organs in the dermis such as 1992). This information has allowed an initial characterhair follicles, Pacinian corpuscles, Ruffini corpuscles, ization of sensory neuron loss in settings where neuro-Meissners corpuscles, and Merkel cells. These DRG trophin or neurotrophin receptor function has been neurons have small-and medium-sized somas with myblocked by antibodies or gene targeting (for review, see elinated axons and spinal projections that terminate in Snider, 1994). To date, however, the neurotrophin dethe deep dorsal horn (see Brown, 1981). To date, howpendence of several classes of DRG neurons has reever, no good histochemical markers have been demained obscure. In this issue of Neuron, Airaksinen et scribed that specifically identify these populations. It al. characterize the neurotrophin requirements of two was predicted that low threshold mechanoreceptive classes of cutaneous mechanoreceptive neurons. Furneurons would require brain-derived neurotrophic factor ther, these investigators present evidence for previously (BDNF) for survival since the BDNF receptor, TrkB, is unappreciated complexities of neurotrophin regulation, expressed by a subpopulation of small-to mediumeven in this relatively simple region of the nervous sized DRG neurons (Ernfors et al., 1992; Schecterson system. and Bothwell, 1992; Mu et al., 1993). Also, BDNF mRNA Recent studies of neurotrophin receptor (Trk) localizais synthesized in dermal mesenchyme during develoption in association with known DRG neuron histochemiment in regions sensitive to touch, including the...

The Chemokine Stromal Cell-Derived Factor-1 Regulates the Migration of Sensory Neuron Progenitors

“…Previous findings suggest that DRG neurons coexpress more than one neurotrophin receptor at early stages of development (such as E11 in mouse) (Snider and Wright, 1996). Subsequently, TrkA is needed, in particular, for the development of complete populations of nociceptive DRG neurons, and TrkC is needed for proprioceptive neurons (Kirstein and Farinas, 2002).…”

p75 and TrkA neurotrophin receptors in human skin after spinal cord and peripheral nerve injury, with special reference to sensory corpuscles

“…In any case, present results suggest that, in addition to other growth factors (for a review see Martin, 1997), NGF acting via TrkA or p75 could be involved in the maintenance of epidermis integrity and thus in wound repair. Further studies are necessary to elucidate whether neurotrophins other than NGF, especially neurotrophin-3, also partici-pate in maintenance of normal or severed cutaneous, nerves, sensory corpuscles, and nonnervous tissues (Zhou and Rush, 1995;Airaksinen et al, 1996;Albers et al, 1996;Snider and Wright, 1996).…”

ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons

“…Consequently, there is an intense interest in elucidating mechanisms for NT-mediated neuroprotection and its contribution to the development of the CNS. NTs including nerve growth factor, brain-derived neurotrophic factor (BDNF), NT3, NT4͞5, and NT6 bind to and activate specific receptor tyrosine kinases of the Trk family (7,8). Upon binding to and activating Trk, NTs can activate several intracellular signaling transduction systems including the phosphatidylinositol 3-kinase, protein kinase C, and extracellular signal-regulated kinase 1͞2 (ERK1͞2) pathways (8-11).…”