Merkel Cells as Putative Regulatory Cells in Skin Disorders: An In Vitro Study

Merkel cells (MCs) are involved in mechanoreception, but several lines of evidence suggest that they may also participate in skin disorders through the release of neuropeptides and hormones. In addition, MC hyperplasias have been reported in inflammatory skin diseases. However, neither proliferation nor reactions to the epidermal environment have been demonstrated. We established a culture model enriched in swine MCs to analyze their proliferative capability and to discover MC survival factors and modulators of MC neuroendocrine properties. In culture, MCs reacted to bFGF by extending outgrowths. Conversely, neurotrophins failed to induce cell spreading, suggesting that they do not act as a growth factor for MCs. For the first time, we provide evidence of proliferation in culture through Ki-67 immunoreactivity. We also found that MCs reacted to histamine or activation of the proton gated/osmoreceptor TRPV4 by releasing vasoactive intestinal peptide (VIP). Since VIP is involved in many pathophysiological processes, its release suggests a putative regulatory role for MCs in skin disorders. Moreover, in contrast to mechanotransduction, neuropeptide exocytosis was Ca2+-independent, as inhibition of Ca2+ channels or culture in the absence of Ca2+ failed to decrease the amount of VIP released. We conclude that neuropeptide release and neurotransmitter exocytosis may be two distinct pathways that are differentially regulated

Immunohistochemical study of cutaneous nerves in the emu

The distribution and chemical content of cutaneous nerves in 3- to 13-day-old emu chicks (Dromaius novaehollandiae) were examined by using double-labelling immunohistochemistry. Seven different subpopulations of cutaneous nerves were identified based on their neurochemistry. No intraepidermal nerve fibres were found. However, axons were located within the dermis and were often associated with blood vessels, pennamotor muscles and feather follicles or innervated Herbst corpuscles. Both similarities and differences exist between subpopulations of cutaneous nerves in the emu and volant birds. As in volant birds, a subpopulation of cutaneous axons innervates the superficial skin layers and contains immunoreactivity to both substance P and calcitonin gene-related peptide (CGRP). This suggests that the neuropeptide content of these presumptive free nerve endings is conserved throughout the evolution of birds. In contrast, Herbst corpuscles in the emu are innervated by axons that contain immunoreactivity for CGRP or neuropeptide Y (NPY) but that lack the calbindin D-28k immunoreactivity found in fibres innervating Herbst corpuscles of volant birds. Herbst corpuscles therefore may have a different chemical content in a flightless species from that in volant birds

A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs

We have used conditional knockout strategies in mice to determine the developmental events and gene expression program regulated by the LIM-homeodomain factor Islet1 in developing sensory neurons. Early development of the trigeminal and dorsal root ganglia are grossly normal in the absence of Islet1. However, from E12.5 onward, Islet1 mutant embryos exhibit loss of the nociceptive markers TrkA and Runx1 and a near absence of cutaneous innervation. Proprioceptive neurons characterized by the expression of TrkC/Runx3/Etv1 are relatively spared. Microarray analysis of Islet1 mutant ganglia reveals prolonged expression of developmental regulators normally restricted to early sensory neurogenesis, and ectopic expression of transcription factors normally found in the CNS but not in sensory ganglia. Later excision of Islet1 does not reactivate early genes, but results in decreased expression of transcripts related to specific sensory functions. Together these results establish a central role for Islet1 in the transition from sensory neurogenesis to subtype specification