NEUROTROPHIN-4 IS REQUIRED FOR THE SURVIVAL OF A SUBCLASS OF HAIR FOLLICLE RECEPTORS

Neurotrophin-4 (NT4) is the most recently discovered neurotrophic fact or in mammals and, functionally the least well understood. Here, we us ed mice that lack NT4 to determine whether NT4 is required for the sur vival of functionally identified subclasses of cutaneous sensory neuro ns. By using three independent methods of histological and electrophys iological analysis, we show that NT4 is specifically required for the survival of down hair (D-hair) receptors that innervate a subpopulatio n of hair follicles. All other functionally distinct types of afferent s neurons innervating hairy skin were not affected in their survival o r in their function. Previous studies have shown that BDNF is required for the mechanical sensitivity of slowly adapting (SA) mechanorecepto rs 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 sho w that the two trkB ligands, NT4 and BDNF, have distinct and nonoverla pping roles in supporting cutaneous sensory neurons. Whereas NT4 is re quired for the survival of D-hair receptors, BDNF supports the mechani cal function of SA fibers.