Neurotrophin 4 is required for the survival of a subclass of hair follicle receptors.

Neurotrophin-4 (NT4) is the most recently discovered neurotrophic factor in mammals and, functionally, the least well understood. Here, we used mice that lack NT4 to determine whether NT4 is required for the survival of functionally identified subclasses of cutaneous sensory neurons. By using three independent methods of histological and electrophysiological analysis, we show that NT4 is specifically required for the survival of down hair (D-hair) receptors that innervate a subpopulation of hair follicles. All other functionally distinct types of afferents neurons innervating hairy skin were not affected in their survival or in their function. Previous studies have shown that BDNF is required for the mechanical sensitivity of slowly adapting (SA) mechanoreceptors but not for the postnatal survival of myelinated cutaneous afferent fibers. In contrast, the receptive properties of SA mechanoreceptors were not impaired in animals lacking NT4. Consequently, these data show that the two trkB ligands, NT4 and BDNF, have distinct and nonoverlapping roles in supporting cutaneous sensory neurons. Whereas NT4 is required for the survival of D-hair receptors, BDNF supports the mechanical function of SA fibers.