DOCSLIB.ORG

The Gentle Touch Receptors of Mammalian Skin Amanda Zimmerman Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Gentle Touch Receptors of Mammalian Skin Amanda Zimmerman Et Al SKIN REVIEW localization and movement and to define tex- tural components of taste. In mammalian fe- males, milk secretion is triggered by suckling stimulation of the nipples. Moreover, some spe- The gentle touch receptors cies have evolved skin that is highly specialized for particular functions. Mystacial pads of noc- of mammalian skin turnalrodentshavelongwhiskersandarespe- cialized for navigation and spatial orientation. Amanda Zimmerman,1 Ling Bai,1,2 David D. Ginty1* The snouts of star-nosed moles and the bills of tactile-foraging birds are specialized for locating prey. These particular skin regions are asso- The skin is our largest sensory organ, transmitting pain, temperature, itch, and ciated with different combinations of LTMRs, touch information to the central nervous system. Touch sensations are conveyed by making each region neurophysiologically and distinct combinations of mechanosensory end organs and the low-threshold functionally distinct. mechanoreceptors (LTMRs) that innervate them. Here we explore the various Key to our understanding of the neuro- structures underlying the diverse functions of cutaneous LTMR end organs. Beyond biological basis of touch is determining how anchoring of LTMRs to the surrounding dermis and epidermis, recent evidence LTMR end organs encode complex forms of suggests that the non-neuronal components of end organs play an active role in tactile stimulation and how this encoding is signaling to LTMRs and may physically gate force-sensitive channels in these then integrated and processed within the cen- receptors. Combined with LTMR intrinsic properties, the balance of these factors tral nervous system. LTMR subtype central pro- comprises the response properties of mechanosensory neurons and, thus, the jections terminate within somatotopic columns neural encoding of touch. in the dorsal horn of the spinal cord, with a sub- set also sending collaterals to he skin, our largest organ, encompasses the dorsal column nuclei of the the entire body and mediates our sense of brainstem (1). Dorsal horn col- touch. Neurophysiologically complex, the umns contain interneurons that T skin is innervated by a wide variety of sen- are thought to process touch on August 3, 2015 sory neuron subtypes, including nocicep- information, as well as projec- tors, which sense painful stimuli; pruriceptors, tion neurons that carry this which convey itch; thermoreceptors, which reg- processed information to the ister temperature information; and low-threshold brainstem and higher cortical mechanoreceptors (LTMRs), which encode non- areas [for a review of central painful mechanical stimuli, or touch. We use our processing, see (2)]. Here we sense of touch to recognize and manipulate ob- explore the mechanosensory end jects, to communicate and socially interact with organs of the skin, focusing on one another, to appreciate the textures of the the physiological, morphological, foods we eat, for procreation and sexual plea- and ultrastructural properties www.sciencemag.org sure, and in maternal nursing. The cutaneous of LTMRs and their associated end organs and the mechanosensory neurons non-neuronal cells, and we hy- that innervate them have evolved to underlie a pothesize how different end range of sensory functions, as evidenced by the organs give rise to the distinct multitude of skin type specializations that are response properties and func- each innervated by a distinct array of sensory tions that define mammalian neuron subtypes, reflecting the diversity of func- touch neurons. tions of touch neurons. Downloaded from Mammalian skin comprises both hairy and LTMRs of hairy and nonhairy, or glabrous, skin. Glabrous skin is glabrous skin predominantly found on the hands and feet of TheLTMRsareaheterogeneous most mammals. In this context, glabrous skin group of sensory neurons. Just is specialized for discriminative touch, deter- Fig. 1. LTMR innervation of glabrous skin. Glabrous skin is in- as the gustatory system has dis- mining texture and shape to accurately recognize nervated by Ab LTMRs, including Ab SA1-LTMRs terminating in tinct sensory receptors optimal- objects and providing feedback to the central Merkel cells, Ab SA2-LTMRs hypothesized to end in Ruffini end- ly tuned to detect sweet, sour, nervous system to mediate proper grip con- ings, Ab RA1-LTMRs innervating Meissner corpuscles, and Ab salty, umami, or bitter tastants, trol, reaching, and locomotion. Hairy skin cov- RA2-LTMRs ending in Pacinian corpuscles. Green boxed regions LTMRs are divided into subtypes ers more than 90% of the body surface. It also are shown in greater detail in Fig. 3 (here, the letters “A,”“B,” and distinguished by their distinct serves a discriminative touch role, albeit with “C” correspond to panels with the same names in Fig. 3). SC, sensitivities, conduction veloc- considerably lower spatial acuity as compared stratum corneum; SL, stratum lucidum; SG, stratum granulosum; ities, and adaptation to sustained with nonhairy skin. Hairy skin is strongly as- SS, stratum spinosum; SB, stratum basale. mechanical stimulation. For ex- sociated with affective touch—that is, touch that ample, slowly-adapting (SA) touch evokes an emotional response, such as during receptors are indentation de- nurturing. Other types of skin are highly spe- tectors, firing continuously during a sustained 1Department of Neurobiology, Howard Hughes Medical cialized for the functional roles they play. The stimulus, whereas rapidly-adapting (RA) touch Institute, Harvard Medical School, 220 Longwood Avenue, genitalia, specifically the glans penis and glans receptors are velocity detectors that respond Boston, MA 02115, USA. 2The Solomon H. Snyder clitoris, are specialized forms of glabrous skin, only to the onset and offset of indentation. In Department of Neuroscience and Howard Hughes Medical fine-tuned for sexual pleasure sensation and re- glabrous skin, four types of LTMRs with fast Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. productive reflexes. The skin of the lips, tongue, conduction velocity (Ab LTMRs) have been *Corresponding author. E-mail: [email protected] and inner cheeks are specialized to aid in food defined (Fig. 1), each with a distinct terminal 950 21 NOVEMBER 2014 • VOL 346 ISSUE 6212 sciencemag.org SCIENCE morphology and tuning property (3–5): (i) Ab SA1-LTMRs innervate Merkel cells in the basal epidermis and report the static nature of touch stimuli, (ii) Ab SA2-LTMRs are hypothesized to terminate in Ruffini corpuscles in the dermis and are particularly sensitive to skin stretch, (iii) Ab RA1-LTMRs innervate Meissner’s corpuscles in dermal papillae and are sensitive to movement across the skin, and (iv) Ab RA2-LTMRs terminate in Pacinian corpuscles deep in the dermis and are tuned to high- frequency vibration (6–8). In hairy skin, several LTMRs form specialized terminals asso- ciated with hair follicles, allow- ing the sense of touch to extend beyond the skin surface (Fig. 2). Ab SA1-LTMRs and Merkel cells form complexes called touch domes to detect skin indentation (9, 10). Thehairfollicleshaftissupplied by collars of mechanoreceptor ter- minals, including at least three LTMR subtypes that exhibit lon- gitudinal lanceolate endings and Fig. 2. LTMR innervation of hairy skin. Hairy skin in rodents is innervated by distinct combinations of LTMRs. Touch onetypethathascircumferen- domes of Merkel cells and associated Ab SA1-LTMRs are found above the level of the sebaceous glands of guard hair tial endings. These subtypes differ follicles. Guard hairs are also innervated by Ab RA-LTMR lanceolate endings. Awl/auchene hairs are innervated by all three in their sensitivities, adaptation types of lanceolate-ending LTMRs: Ab RA-LTMRs, Ad-LTMRs, and C-LTMRs. Zigzag hairs, the most numerous, are innervated properties, and conduction veloc- by Ad-LTMRs and C-LTMRs. Circumferential endings encircle the longitudinal lanceolate endings of all three types of hair ities (1, 11). The neck of the hair follicles. The white boxed region is shown in greater detail in Fig. 4. follicles and the adjacent epidermis are penetrated by unmyelinated LTMRs with free nerve endings (12). At least one These complexes are infrequent or absent in dense-core vesicles are hypothesized to release type of unmyelinated, slowly-conducting LTMR skin regions in which spatial acuity is not para- neuropeptides rather than classical neurotrans- has endings localized solely to hairy skin and is mount, such as the genitalia (15, 16). Ab SA1- mitters, thus modulating Ab SA1-LTMR responses. implicated in pleasurable touch sensation in LTMR responses to static indentation include Taste receptor cells in the gustatory system humans (13). Thus, morphological and neuro- a high-frequency dynamic phase during initial and hair cells of the auditory system are promi- physiological differences in glabrous- and hairy- skin indentation and lower-frequency, tonic nent examples of non-neuronal cells participat- skin LTMRs define the distinct sensory functions firing during prolonged indentation. Function- ing in stimulus transduction (21, 22), yet it was of glabrous and hairy skin. ally, studies mainly performed in humans and only recently shown that an analogous situation other primates indicate that the glabrous-skin occurs in touch sensation. Merkel cells, both in The form that underlies function Merkel cell/Ab SA1-LTMR complex conveys in- culture and ex vivo, exhibit mechanically acti- of cutaneous touch receptors formation about texture,
Load more

Recommended publications
  • Chemoreception
    Senses 5 SENSES live version • discussion • edit lesson • comment • report an error enses are the physiological methods of perception. The senses and their operation, classification, Sand theory are overlapping topics studied by a variety of fields. Sense is a faculty by which outside stimuli are perceived. We experience reality through our senses. A sense is a faculty by which outside stimuli are perceived. Many neurologists disagree about how many senses there actually are due to a broad interpretation of the definition of a sense. Our senses are split into two different groups. Our Exteroceptors detect stimulation from the outsides of our body. For example smell,taste,and equilibrium. The Interoceptors receive stimulation from the inside of our bodies. For instance, blood pressure dropping, changes in the gluclose and Ph levels. Children are generally taught that there are five senses (sight, hearing, touch, smell, taste). However, it is generally agreed that there are at least seven different senses in humans, and a minimum of two more observed in other organisms. Sense can also differ from one person to the next. Take taste for an example, what may taste great to me will taste awful to someone else. This all has to do with how our brains interpret the stimuli that is given. Chemoreception The senses of Gustation (taste) and Olfaction (smell) fall under the category of Chemoreception. Specialized cells act as receptors for certain chemical compounds. As these compounds react with the receptors, an impulse is sent to the brain and is registered as a certain taste or smell. Gustation and Olfaction are chemical senses because the receptors they contain are sensitive to the molecules in the food we eat, along with the air we breath.
    [Show full text]
  • The Roles and Functions of Cutaneous Mechanoreceptors Kenneth O Johnson
    455 The roles and functions of cutaneous mechanoreceptors Kenneth O Johnson Combined psychophysical and neurophysiological research has nerve ending that is sensitive to deformation in the resulted in a relatively complete picture of the neural mechanisms nanometer range. The layers function as a series of of tactile perception. The results support the idea that each of the mechanical filters to protect the extremely sensitive recep- four mechanoreceptive afferent systems innervating the hand tor from the very large, low-frequency stresses and strains serves a distinctly different perceptual function, and that tactile of ordinary manual labor. The Ruffini corpuscle, which is perception can be understood as the sum of these functions. located in the connective tissue of the dermis, is a rela- Furthermore, the receptors in each of those systems seem to be tively large spindle shaped structure tied into the local specialized for their assigned perceptual function. collagen matrix. It is, in this way, similar to the Golgi ten- don organ in muscle. Its association with connective tissue Addresses makes it selectively sensitive to skin stretch. Each of these Zanvyl Krieger Mind/Brain Institute, 338 Krieger Hall, receptor types and its role in perception is discussed below. The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218-2689, USA; e-mail: [email protected] During three decades of neurophysiological and combined Current Opinion in Neurobiology 2001, 11:455–461 psychophysical and neurophysiological studies, evidence has accumulated that links each of these afferent types to 0959-4388/01/$ — see front matter © 2001 Elsevier Science Ltd. All rights reserved. a distinctly different perceptual function and, furthermore, that shows that the receptors innervated by these afferents Abbreviations are specialized for their assigned functions.
    [Show full text]
  • Branched Cells in the Epidermis: an Overview
    0022-202X/ 80/ 7501-0006$02.00/0 THE JOURNAL OF INVESTIGATIVE D ERMATOLOGY, 75:6-11, 1980 Vol. 75, No.1 Copyrighl © 1980 by The Williams & Wilkins Co. Printed in U.S.A. Branched Cells in the Epidermis: An Overview A. S. BREATHNACH, M.Sc., M.D. Department of Anatomy, St. Mary's Hospital Medical School (University of London), London, W.2, UK Current knowledge concerning the nature, lineage, due, no doubt, to overconcentration upon their own pet clear and function of the Langerhans cell, Merkel cell, and, to cells, to the fact that no specific stains for lymphocytes had a lesser extent, the melanocyte, are reviewed under been evolved, to the unacceptability of Andrew's conclusions headings that emphasize the confederate constitution of [ 4] that lymphocytes were capable of differentiating into prac­ the epidermis as a compound tissue composed of a vari­ tically every other variety of epidermal cell, and finally to the ety of cellular elements; the role of the lymphocyte as a lack of an obvious reason for their presence there at all under component of normal epidermis is also considered. It normal circumstances. appears that the function of the Langerhans cell has Today; a further 20 yr along the way, this question of intrae­ finally been established, i.e., it serves as a front-line pidermallymphocytes has become an issue of vital importance, element in immune reactions of the skin. Develop­ not only in relation to individual immunopathologic situations, mentally, it is of mesenchymal origin. The Merkel cell but also from the wider points of view put forward by Fichthel­ still presents a number of problems centering around ius, Groth, and Liden [5] and Streilein [6] in connection with questions of its lineage, the nature of its characteristic the skin as an immunologic inductive microenvironment, and granules, and the "synaptic" relationship between it and the possible existence of a subpopulation of lymphocytes sub­ the associated neurite.
    [Show full text]
  • Diversification and Specialization of Touch Receptors in Skin
    Downloaded from http://perspectivesinmedicine.cshlp.org/ on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Diversification and Specialization of Touch Receptors in Skin David M. Owens1,2 and Ellen A. Lumpkin1,3 1Department of Dermatology, Columbia University College of Physicians and Surgeons, New York, New York 10032 2Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032 3Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032 Correspondence: [email protected] Our skin is the furthest outpost of the nervous system and a primary sensor for harmful and innocuous external stimuli. As a multifunctional sensory organ, the skin manifests a diverse and highly specialized array of mechanosensitive neurons with complex terminals, or end organs, which are able to discriminate different sensory stimuli and encode this information for appropriate central processing. Historically, the basis for this diversity of sensory special- izations has been poorly understood. In addition, the relationship between cutaneous me- chanosensory afferents and resident skin cells, including keratinocytes, Merkel cells, and Schwann cells, during the development and function of tactile receptors has been poorly defined. In this article, we will discuss conserved tactile end organs in the epidermis and hair follicles, with a focus on recent advances in our understanding that have emerged from studies of mouse hairy skin. kin is our body’s protective covering and skills, including typing, feeding, and dressing Sour largest sensory organ. Unique among ourselves. Touch is also important for social ex- our sensory systems, the skin’s nervous system change, including pair bonding and child rear- www.perspectivesinmedicine.org gives rise to distinct sensations, including gentle ing (Tessier et al.
    [Show full text]
  • Merkel Cell Carcinoma
    Case Report Merkel cell carcinoma Eiman Nasseri MD FRCPC erkel cell carcinoma (MCC) is a rare yet highly aggressive tumour of the skin. While the dangers of other skin Mcancers like malignant melanoma are ingrained in most physicians’ minds—with the changing or atypical nevus often inciting an urgent biopsy—MCC remains an unfamiliar and neglected disease. Yet, the annual incidence of MCC is rising more quickly than that of melanoma, at 8% annually, and one-third of patients die within 3 years of diagno- sis.1,2 Despite these sobering figures, a timely diagnosis followed by exci- sion and radiotherapy can be curative in early disease. This article seeks EDITor’s KEY POINTS to familiarize family physicians with both the characteristics and the man- • Merkel cell carcinoma (MCC) is a rare but agement of MCC, so that they can quickly identify MCC patients and direct highly aggressive cutaneous neoplasm with a them to the appropriate specialists for care. rising incidence among elderly patients. The 3-year mortality rate is greater than 30%, Case description surpassing that of malignant melanoma. A 93-year-old white woman presented to the emergency department with an asymptomatic tumour on her left ear (Figure 1). She claimed that the lesion • The most common clinical features had appeared 2 months earlier and had been growing rapidly. The patient of MCC have been summarized by the was otherwise healthy and not taking any medications. On physical exami- acronym AEIOU: asymptomatic, expanding nation, her skin showed moderate photodamage. A 5- by 4-cm erythema- rapidly, immunosuppression, older than 50 tous, dome-shaped nodule was noted in her left conchal bowl.
    [Show full text]
  • Diagnostic Accuracy of a Panel of Immunohistochemical and Molecular Markers to Distinguish Merkel Cell Carcinoma from Other Neuroendocrine Carcinomas
    Modern Pathology (2019) 32:499–510 https://doi.org/10.1038/s41379-018-0155-y ARTICLE Diagnostic accuracy of a panel of immunohistochemical and molecular markers to distinguish Merkel cell carcinoma from other neuroendocrine carcinomas 1,2,3 4 1 3 3 Thibault Kervarrec ● Anne Tallet ● Elodie Miquelestorena-Standley ● Roland Houben ● David Schrama ● 5 2 6 7 8 Thilo Gambichler ● Patricia Berthon ● Yannick Le Corre ● Ewa Hainaut-Wierzbicka ● Francois Aubin ● 9 10 11 12 12 Guido Bens ● Flore Tabareau-Delalande ● Nathalie Beneton ● Gaëlle Fromont ● Flavie Arbion ● 13 2 2,14 1,2 Emmanuelle Leteurtre ● Antoine Touzé ● Mahtab Samimi ● Serge Guyétant Received: 14 July 2018 / Revised: 2 September 2018 / Accepted: 3 September 2018 / Published online: 22 October 2018 © United States & Canadian Academy of Pathology 2018 Abstract Merkel cell carcinoma is a rare neuroendocrine carcinoma of the skin mostly induced by Merkel cell polyomavirus integration. Cytokeratin 20 (CK20) positivity is currently used to distinguish Merkel cell carcinomas from other neuroendocrine carcinomas. However, this distinction may be challenging in CK20-negative cases and in cases without a 1234567890();,: 1234567890();,: primary skin tumor. The objectives of this study were first to evaluate the diagnostic accuracy of previously described markers for the diagnosis of Merkel cell carcinoma and second to validate these markers in the setting of difficult-to- diagnose Merkel cell carcinoma variants. In a preliminary set (n = 30), we assessed optimal immunohistochemical patterns (CK20, thyroid transcription factor 1 [TTF-1], atonal homolog 1 [ATOH1], neurofilament [NF], special AT-rich sequence- binding protein 2 [SATB2], paired box protein 5, terminal desoxynucleotidyl transferase, CD99, mucin 1, and Merkel cell polyomavirus-large T antigen) and Merkel cell polyomavirus load thresholds (real-time PCR).
    [Show full text]
  • Sensory Receptors A17 (1)
    SENSORY RECEPTORS A17 (1) Sensory Receptors Last updated: April 20, 2019 Sensory receptors - transducers that convert various forms of energy in environment into action potentials in neurons. sensory receptors may be: a) neurons (distal tip of peripheral axon of sensory neuron) – e.g. in skin receptors. b) specialized cells (that release neurotransmitter and generate action potentials in neurons) – e.g. in complex sense organs (vision, hearing, equilibrium, taste). sensory receptor is often associated with nonneural cells that surround it, forming SENSE ORGAN. to stimulate receptor, stimulus must first pass through intervening tissues (stimulus accession). each receptor is adapted to respond to one particular form of energy at much lower threshold than other receptors respond to this form of energy. adequate (s. appropriate) stimulus - form of energy to which receptor is most sensitive; receptors also can respond to other energy forms, but at much higher thresholds (e.g. adequate stimulus for eye is light; eyeball rubbing will stimulate rods and cones to produce light sensation, but threshold is much higher than in skin pressure receptors). when information about stimulus reaches CNS, it produces: a) reflex response b) conscious sensation c) behavior alteration SENSORY MODALITIES Sensory Modality Receptor Sense Organ CONSCIOUS SENSATIONS Vision Rods & cones Eye Hearing Hair cells Ear (organ of Corti) Smell Olfactory neurons Olfactory mucous membrane Taste Taste receptor cells Taste bud Rotational acceleration Hair cells Ear (semicircular
    [Show full text]
  • Merkel Cell Carcinoma: Update and Review Timothy S
    Merkel Cell Carcinoma: Update and Review Timothy S. Wang, MD,* Patrick J. Byrne, MD, FACS,† Lisa K. Jacobs, MD,‡ and Janis M. Taube, MD§ Merkel cell carcinoma (MCC) is a rare, aggressive, and often fatal cutaneous malignancy that is not usually suspected at the time of biopsy. Because of its increasing incidence and the discovery of a possible viral association, interest in MCC has escalated. Recent effort has broadened our breadth of knowledge regarding MCC and developed instruments to improve data collection and future study. This article provides an update on current thinking about the Merkel cell and MCC. Semin Cutan Med Surg 30:48-56 © 2011 Elsevier Inc. All rights reserved. erkel cell carcinoma (MCC) is a rare, aggressive, and current thinking, including novel insights into the Merkel Moften fatal cutaneous malignancy. It usually presents as cell; a review of the 2010 National Comprehensive Cancer a banal-appearing lesion and the diagnosis is rarely suspected Network (NCCN) therapeutic guidelines and new American at the time of biopsy. Because of increasing incidence and the Joint Committee on Cancer (AJCC) staging system; recom- discovery of a possible viral association, interest in MCC has mendations for pathologic reporting and new diagnostic escalated rapidly. codes; and the recently described Merkel cell polyoma virus From 1986 to 2001, the incidence of MCC in the United (MCPyV). States has tripled, and approximately 1500 new cases are diagnosed each year.1,2 MCC occurs most frequently among elderly white patients and perhaps slightly more commonly History in men. MCCs tend to occur on sun-exposed areas, with Merkel cells (MCs) were first described by Friedrich Merkel 3 nearly 80% presenting on the head, neck, and extremities.
    [Show full text]
  • Merkel Cell Carcinoma of the Forehead Area: a Literature Review and Case Report
    Oral and Maxillofacial Surgery (2019) 23:365–373 https://doi.org/10.1007/s10006-019-00793-y CASE REPORT Merkel cell carcinoma of the forehead area: a literature review and case report Claudio Caldarelli1 & Umberto Autorino2 & Caterina Iaquinta1 & Andrea De Marchi3 Received: 15 September 2018 /Accepted: 10 July 2019 /Published online: 24 July 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Background Merkel cell carcinoma (MCC) is an uncommon, aggressive malignancy of the skin, mostly affecting head and neck area in elderly white patients. Between head/neck sites, face accounts for 61% and forehead accounts for 17% of all face MCCs. Purpose We here present a literature review MCC cases arising in the forehead area, published in the English literature in the period 1987–2018, and report a personal observation with a late diagnosis and a treatment out of the current recommendations. The aims of this paper are to provide an up-to-date on MCC arising in the forehead area and to raise awareness about misdiag- nosis of this type of lesion mimicking arteriovenous malformations (AVM). Material and method Literature review was performed on PubMed and Medline database and “Merkel cell carcinoma (MCC),” “forehead” and “MCC forehead location” were the terms the authors searched for. Patients’ data have been drawn from descrip- tions of single cases and of short case series reports. For each case, data were collected about clinical characteristics, treatment modalities and outcomes. The study has been limited to the clinical features of the disease, excluding etiologic/pathogenic aspects. Results Twenty-five patients with forehead MCC have been identified, coming from 20 sources.
    [Show full text]
  • Piezo2 in Cutaneous and Proprioceptive Mechanotransduction in Vertebratesa
    ARTICLE IN PRESS Piezo2 in Cutaneous and Proprioceptive Mechanotransduction in Vertebratesa E.O. Anderson, E.R. Schneider and S.N. Bagriantsev1 Yale University, New Haven, CT, United States 1Corresponding author: E-mail: [email protected] Contents 1. Introduction 2 2. Somatosensory Neurons 4 2.1 Piezo2 and fast mechanoactivated current in mouse dorsal root ganglia 4 neurons 2.2 Possible role of Piezo2 in slow mechanoactivated current 6 2.3 Functional regulation of Piezo2 in mouse dorsal root ganglia neurons 7 3. Light Touch 8 3.1 Insights from mice 8 3.2 Insight from other vertebrates 9 4. Proprioception 11 5. Merkel Cells 12 6. Nociception 14 7. Conclusions and Perspectives 16 References 16 Abstract Mechanosensitivity is a fundamental physiological capacity, which pertains to all life forms. Progress has been made with regard to understanding mechanosensitivity in bacteria, flies, and worms. In vertebrates, however, the molecular identity of mechanotransducers in a This work was supported by grants from National Science Foundation (1453167), National Institutes of Health (1R01NS097547-01A1) and American Heart Association (14SDG17880015) to S.N.B. E.R.S. was partially supported by a training grant from National Institutes of Health T32HD007094 and a postdoctoral fellowship from the Arnold and Mabel Beckman Foundation. E.O.A. is a fellow of The Gruber Foundation and an Edward L. Tatum Fellow. Correspondence should be addressed to S.N.B ([email protected]). Current Topics in Membranes, Volume 79 ISSN 1063-5823 © 2016 Elsevier Inc. http://dx.doi.org/10.1016/bs.ctm.2016.11.002 All rights reserved.
    [Show full text]
  • Nerve Endings Associated with the Merkel Cell-Neurite Complex in the Lesional Oral Mucosa Epithelium of Lichen Planus and Hyperkeratosis
    International Journal of Oral Science (2016) 8, 32–38 OPEN www.nature.com/ijos ORIGINAL ARTICLE Loss of Ab-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis Daniela Caldero´n Carrio´n1,Yu¨ksel Korkmaz1,2,3, Britta Cho2, Marion Kopp1, Wilhelm Bloch4, Klaus Addicks3 and Wilhelm Niedermeier1 The Merkel cell-neurite complex initiates the perception of touch and mediates Ab slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Ab- and Ad-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium.
    [Show full text]
  • Merkel Cell Carcinoma: a Review
    Merkel Cell Carcinoma: A Review Christian W. Oram, DO; Cynthia L. Bartus, MD; Stephen M. Purcell, DO PRACTICE POINTS • Merkel cell carcinoma has been associated with a novel polyomavirus. • Merkel cell carcinoma follows a very aggressive course and is most likely metastatic at diagnosis. Merkel cell carcinoma (MCC) is a rare neuro- Tumor cells havecopy been linked to the amine precur- endocrine tumor of unknown origin that usu- sor uptake and decarboxylation system.3 In 1972, ally presents in the elderly population. A novel Toker4 described several cases of trabecular or sweat polyomavirus has been associated with a large gland carcinomas of the skin. Upon further inves- percentage of tumors. Immune response plays tigation,not the cells that comprised these tumors an important role in pathogenesis of MCC. This were found to have dense core granules on elec- article reviews the history, pathogenesis, presen- tron microscopy, typical of Merkel cells.1,2 Other tation, and treatment of MCC. Future treatments terms such as neuroendocrine carcinoma of the skin, also are discussed briefly. Dosmall cell carcinoma of the skin, and anaplastic Cutis. 2016;97:290-295. carcinoma of the skin have been used to describe Merkel cell carcinoma (MCC),1 which was suggested by De Wolf-Peeters et al5 in 1980. erkel cells originally were described by Despite being a rare malignancy, MCC follows German histopathologist Friedrich Sigmund an aggressive clinical course. Upon presentation, MMerkel in 1875. These unique tactile cells approximately 66% of patients have local disease, were described as epidermal, nondendritic, and non- 27% have nodal involvement, and 7% have dis- keratinizing.
    [Show full text]