Talk:Sensory - Touch Development
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Cite this page: Hill, M.A. (2024, April 26) Embryology Sensory - Touch Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Sensory_-_Touch_Development |
2018
Logan GJ, Wright MC, Kubicki AC & Maricich SM. (2018). Notch pathway signaling in the skin antagonizes Merkel cell development. Dev. Biol. , 434, 207-214. PMID: 29241683 DOI.
Merkel cells are mechanosensitive skin cells derived from the epidermal lineage whose development requires expression of the basic helix-loop-helix transcription factor Atoh1. The genes and pathways involved in regulating Merkel cell development during embryogenesis are poorly understood. Notch pathway signaling antagonizes Atoh1 expression in many developing body regions, so we hypothesized that Notch signaling might inhibit Merkel cell development. We found that conditional, constitutive overexpression of the Notch intracellular domain (NICD) in mouse epidermis significantly decreased Merkel cell numbers in whisker follicles and touch domes of hairy skin. Conversely, conditional deletion of the obligate NICD binding partner RBPj in the epidermis significantly increased Merkel cell numbers in whisker follicles, led to the development of ectopic Merkel cells outside of touch domes in hairy skin epidermis, and altered the distribution of Merkel cells in touch domes. Deletion of the downstream Notch effector gene Hes1 also significantly increased Merkel cell numbers in whisker follicles. Together, these data demonstrate that Notch signaling regulates Merkel cell production and patterning. KEYWORDS: Development; Skin; Somatosensation PMID: 29241683 DOI: 10.1016/j.ydbio.2017.12.007 [Indexed for MEDLINE]
The development of human digital Meissner's and Pacinian corpuscles
Ann Anat. 2018 May 26;219:8-24. doi: 10.1016/j.aanat.2018.05.001. [Epub ahead of print]
Feito J1, García-Suárez O2, García-Piqueras J2, García-Mesa Y2, Pérez-Sánchez A3, Suazo I4, Cabo R2, Suárez-Quintanilla J5, Cobo J6, Vega JA7.
Abstract
Meissner's and Pacinian corpuscles are cutaneous mechanoreceptors responsible for different modalities of touch. The development of these sensory formations in humans is poorly known, especially regarding the acquisition of the typical immunohistochemical profile related to their full functional maturity. Here we used a panel of antibodies (to specifically label the main corpuscular components: axon, Schwann-related cells and endoneurial-perineurial-related cells) to investigate the development of digital Meissner's and Pacinian corpuscles in a representative sample covering from 11 weeks of estimated gestational age (wega) to adulthood. Development of Pacinian corpuscles starts at 13 wega, and it is completed at 4 months of life, although their basic structure and immunohistochemical characteristics are reached at 36 wega. During development, around the axon, a complex network of S100 positive Schwann-related processes is progressively compacted to form the inner core, while the surrounding mesenchyme is organized and forms the outer core and the capsule. Meissner's corpuscles start to develop at 22 wega and complete their typical morphology and immunohistochemical profile at 8 months of life. In developing Meissner's corpuscles, the axons establish complex relationships with the epidermis and are progressively covered by Schwann-like cells until they complete the mature arrangement late in postnatal life. The present results demonstrate an asynchronous development of the Meissner's and Pacini's corpuscles and show that there is not a total correlation between morphological and immunohistochemical maturation. The correlation of the present results with touch-induced cortical activity in developing humans is discussed. KEYWORDS: Development; Glabrous skin; Human; Meissner’s corpuscles; Pacinian corpuscles; Sensory corpuscles PMID: 29842990 DOI: 10.1016/j.aanat.2018.05.001
Tree of Vater-Pacinian corpuscles in the human finger and thumb: a comparison between the late fetal stage and old age
Surg Radiol Anat. 2018 Mar;40(3):243-257. doi: 10.1007/s00276-017-1894-z. Epub 2017 Jun 26.
Kobayashi K1, Cho KH2, Yamamoto M1, Mitomo K1, Murakami G1,3, Abe H4, Abe S1.
Abstract Using histological sections of 12 hands from 12 human fetuses at 20-34 weeks of gestation (150-290 mm) and 14 fingers (index and small) from seven donated cadavers of elderly individuals (aged 78-95 years), we compared the features of Vater-Pacinian corpuscles between these two stages of life. Corpuscles with thin, tightly packed lamellae appeared to undergo a change to thick, loosely packed lamellae at 23-32 weeks. The typical fetal corpuscle had two parts: (1) a rod-like proximal part (0.2-0.6 mm in length) extending along the proximodistal axis of the finger, and (2) a distal end (0.1 mm) after acute bending of the proximal part. Corpuscles were associated with palmar digital nerves in the fingers, but were also present along the dorsal nerves in the thumb. A flower bouquet- or tree-like arrangement including 5-10 corpuscles extended to the dermis of the skin along a perforating artery. Serial sections of the thumb and fifth finger revealed approximately 80-180 corpuscles in the distal phalangeal segment. In elderly individuals, the corpuscles were distributed along the palmar digital nerve, but (1) their density was much lower than in fetuses and (2) a bouquet- or tree-like arrangement was rarely seen. In the distal segment, there were fewer than 40 adult corpuscles, being 0.2-0.5 mm thick and 1.0-2.5 mm long. Wavy or coiled corpuscles were evident. Because of the considerable differences in the distribution and number of corpuscles between the fetus and adult, they appear to undergo considerable depletion with age, especially along thin, superficial nerve branches. KEYWORDS: Distribution; Elderly cadaver; Hand; Human fetus; Palmar digital nerves; Vater–Pacinian corpuscles PMID: 28653179 DOI: 10.1007/s00276-017-1894-z
Developmental changes in the perception of visuotactile simultaneity
J Exp Child Psychol. 2018 Sep;173:304-317. doi: 10.1016/j.jecp.2018.04.014. Epub 2018 May 21.
Chen YC1, Lewis TL2, Shore DI2, Spence C3, Maurer D4.
Abstract
A simultaneity judgment (SJ) task was used to measure the developmental trajectory of visuotactile simultaneity perception in children (aged 7, 9, 11, and 13 years) and adults. Participants were presented with a visual flash in the center of a computer monitor and a tap on their right index finger (located 20° below the flash) with 13 possible stimulus onset asynchronies (SOAs). Participants reported whether the flash and tap were presented at the same time. Compared with the adult group, children aged 7 and 9 years made more simultaneous responses when the tap led by more than 300 ms and when the flash led by more than 200 ms, whereas they made fewer simultaneous responses at the 0 ms SOA. Model fitting demonstrated that the window of visuotactile simultaneity became narrower with development and reached adult-like levels between 9 and 11 years of age. Response errors decreased continuously until 11 years of age. The point of subjective simultaneity (PSS) was located on the tactile-leading side in all participants tested, indicating that 7-year olds (the youngest age tested) are adult-like on this measure. In summary, the perception of visuotactile simultaneity is not fully mature until 11 years of age. The protracted development of visuotactile simultaneity perception may be related to the need for crossmodal recalibration as the body grows and to the developmental improvements in the ability to optimally integrate visual and tactile signals. KEYWORDS: Children; Crossmodal; Development; Multisensory; Touch; Vision PMID: 29783043 DOI: 10.1016/j.jecp.2018.04.014
Pacinian Corpuscles in the Human Fetal Finger and Thumb: A Study Using 3D Reconstruction and Immunohistochemistry
Anat Rec (Hoboken). 2018 Jan;301(1):154-165. doi: 10.1002/ar.23707. Epub 2017 Nov 4.
Kim JH1, Park C2, Yang X3, Murakami G4,5, Abe H5, Shibata S6.
Abstract The detailed distribution of Pacinian corpuscles was evaluated by viewing the transverse sections of all fingers and thumbs, including the interdigital areas, from eight hands of five fetuses of gestational age 28-33 weeks (crown-rump length 230-290 mm). Among the 40 fingers and thumbs, serial sections were prepared for 3D reconstructions of nerve elements in the distal and middle phalangeal segments of three fifth fingers; in these three fingers, the distal segment contained 45-75 Pacinian corpuscles. These Pacinian corpuscles were 0.2-1.0 mm in length and 0.05-0.3 mm in thickness, oriented along the proximodistal axis and arranged along the palmar digital nerve branches. Other than beneath the digital skin, small corpuscles (<0.1 mm in thickness) were observed within the tendon sheath of the flexors in the middle or distal segment of five fetuses and in the nail beds of four fetuses. Clusters of 5-20 corpuscles formed bouquet- or tree-like arrangements along neurovascular bundles in the fingers, thumbs and interdigital areas. Because the space beneath the skin was thick and loose in the interdigital area, trees in the interdigital area were up to 2 mm long. Regardless of site, the central core of each corpuscle was positive for S100 protein, while the core and parts of the capillaries in the corpuscle were weakly positive for nestin. Because corpuscles in the tendon sheath and nail bed, as well as bouquet- and tree-like arrangements of corpuscles, have not been reported in adults, these morphologies are likely specific to fetuses. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:154-165, 2018.
© 2017 Wiley Periodicals, Inc.
KEYWORDS: Pacinian corpuscles; distribution; hand; human fetuses; palmar digital nerves PMID: 29059706 DOI: 10.1002/ar.23707
2016
The development of the nociceptive brain
Neuroscience. 2016 Dec 3;338:207-219. doi: 10.1016/j.neuroscience.2016.07.026. Epub 2016 Jul 22. Verriotis M1, Chang P1, Fitzgerald M2, Fabrizi L1. Author information 1 Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom. 2 Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom. Electronic address: m.fitzgerald@ucl.ac.uk. Abstract This review addresses the fundamental question of how we first experience pain, at the beginning of our lives. The brain is activated by peripheral tissue damaging stimulation from birth, but unlike other sensory systems, the pain system in healthy individuals cannot rely upon prolonged activity-dependent shaping through repeated noxious stimulation. Considering the importance of pain, remarkably little is known about when and how nociceptive cortical network activity characteristic of the mature adult brain develops. We begin this review by considering the underlying framework of connections in the infant brain. Since this developing brain connectome is necessary, if not sufficient, for pain experience, we discuss the structural and functional development of cortical and subcortical networks that contribute to this network. We then review specific information on the development of nociceptive processing in the infant brain, considering evidence from neurophysiological and hemodynamic measures separately, as the two are not always consistent. Finally we highlight areas that require further research and discuss how information gained from laboratory animal models will greatly increase our understanding in this area. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved. KEYWORDS: Somatosensory; connectome; cortex; imaging; infant; pain PMID: 27457037 DOI: 10.1016/j.neuroscience.2016.07.026
Making sense out of spinal cord somatosensory development
Development. 2016 Oct 1;143(19):3434-3448.
Lai HC1, Seal RP2, Johnson JE1.
Abstract
The spinal cord integrates and relays somatosensory input, leading to complex motor responses. Research over the past couple of decades has identified transcription factor networks that function during development to define and instruct the generation of diverse neuronal populations within the spinal cord. A number of studies have now started to connect these developmentally defined populations with their roles in somatosensory circuits. Here, we review our current understanding of how neuronal diversity in the dorsal spinal cord is generated and we discuss the logic underlying how these neurons form the basis of somatosensory circuits.
© 2016. Published by The Company of Biologists Ltd.
KEYWORDS: Cutaneous; Dorsal spinal cord development; Itch; Mechanosensation; Neuroepithelium; Nociception; Pain; Proprioception; Pruriception; Thermosensation; Touch; Transcription factor networks; Vertebrate neural tube
PMID 27702783
A Cascade of Wnt, Eda, and Shh Signaling Is Essential for Touch Dome Merkel Cell Development
PLoS Genet. 2016 Jul 14;12(7):e1006150. doi: 10.1371/journal.pgen.1006150. eCollection 2016.
Xiao Y1, Thoresen DT1, Miao L1, Williams JS1, Wang C2, Atit RP3, Wong SY4, Brownell I1.
Abstract
The Sonic hedgehog (Shh) signaling pathway regulates developmental, homeostatic, and repair processes throughout the body. In the skin, touch domes develop in tandem with primary hair follicles and contain sensory Merkel cells. The developmental signaling requirements for touch dome specification are largely unknown. We found dermal Wnt signaling and subsequent epidermal Eda/Edar signaling promoted Merkel cell morphogenesis by inducing Shh expression in early follicles. Lineage-specific gene deletions revealed intraepithelial Shh signaling was necessary for Merkel cell specification. Additionally, a Shh signaling agonist was sufficient to rescue Merkel cell differentiation in Edar-deficient skin. Moreover, Merkel cells formed in Fgf20 mutant skin where primary hair formation was defective but Shh production was preserved. Although developmentally associated with hair follicles, fate mapping demonstrated Merkel cells primarily originated outside the hair follicle lineage. These findings suggest that touch dome development requires Wnt-dependent mesenchymal signals to establish reciprocal signaling within the developing ectoderm, including Eda signaling to primary hair placodes and ultimately Shh signaling from primary follicles to extrafollicular Merkel cell progenitors. Shh signaling often demonstrates pleiotropic effects within a structure over time. In postnatal skin, Shh is known to regulate the self-renewal, but not the differentiation, of touch dome stem cells. Our findings relate the varied effects of Shh in the touch dome to the ligand source, with locally produced Shh acting as a morphogen essential for lineage specification during development and neural Shh regulating postnatal touch dome stem cell maintenance. PMID 27414798
2015
Comparative analysis of Meissner's corpuscles in the fingertips of primates
J Anat. 2015 Jul;227(1):72-80. doi: 10.1111/joa.12327. Epub 2015 Jun 5.
Verendeev A1, Thomas C1, McFarlin SC1, Hopkins WD2,3, Phillips KA4, Sherwood CC1.
Abstract
Meissner's corpuscles (MCs) are tactile mechanoreceptors found in the glabrous skin of primates, including fingertips. These receptors are characterized by sensitivity to light touch, and therefore might be associated with the evolution of manipulative abilities of the hands in primates. We examined MCs in different primate species, including common marmoset (Callithrix jacchus, n = 5), baboon (Papio anubis, n = 2), rhesus macaque (Macaca mulatta, n = 3), chimpanzee (Pan troglodytes, n = 3), bonobo (Pan paniscus, n = 1) and human (Homo sapiens, n = 8). Fingertips of the first, second and fourth digits were collected from both hands of specimens, dissected and histologically stained using hematoxylin and eosin. The density (MCs per 1 mm(2) ) and the size (cross-sectional diameter of MCs) were quantified. Overall, there were no differences in the densities of MCs or their size among the digits or between the hands for any species examined. However, MCs varied across species. We found a trend for higher densities of MCs in macaques and humans compared with chimpanzees and bonobos; moreover, apes had larger MCs than monkeys. We further examined whether the density or size of MCs varied as a function of body mass, measures of dexterity and dietary frugivory. Among these variables, only body size accounted for a significant amount of variation in the size of MCs. KEYWORDS: Meissner's corpuscles; body mass; dietary frugivory; digital dexterity; primates PMID: 26053332 PMCID: PMC4475360 DOI: 10.1111/joa.12327
Merkel cells and neurons keep in touch
Trends Cell Biol. 2015 Feb;25(2):74-81. doi: 10.1016/j.tcb.2014.10.003. Epub 2014 Dec 2.
Woo SH1, Lumpkin EA2, Patapoutian A3.
Abstract
The Merkel cell-neurite complex is a unique vertebrate touch receptor comprising two distinct cell types in the skin. Its presence in touch-sensitive skin areas was recognized more than a century ago, but the functions of each cell type in sensory transduction have been unclear. Three recent studies demonstrate that Merkel cells are mechanosensitive cells that function in touch transduction via Piezo2. One study concludes that Merkel cells, rather than sensory neurons, are principal sites of mechanotransduction, whereas two other studies report that both Merkel cells and neurons encode mechanical inputs. Together, these studies settle a long-standing debate on whether or not Merkel cells are mechanosensory cells, and enable future investigations of how these skin cells communicate with neurons. Copyright © 2014 Elsevier Ltd. All rights reserved. KEYWORDS: Piezo; mechanoreceptor; mechanosensory cells; somatosensory; touch dome
PMID 25480024
Unipotent, Atoh1+ progenitors maintain the Merkel cell population in embryonic and adult mice
J Cell Biol. 2015 Feb 2;208(3):367-79. doi: 10.1083/jcb.201407101. Epub 2015 Jan 26.
Wright MC1, Reed-Geaghan EG2, Bolock AM3, Fujiyama T4, Hoshino M4, Maricich SM5.
Abstract
Resident progenitor cells in mammalian skin generate new cells as a part of tissue homeostasis. We sought to identify the progenitors of Merkel cells, a unique skin cell type that plays critical roles in mechanosensation. We found that some Atoh1-expressing cells in the hairy skin and whisker follicles are mitotically active at embryonic and postnatal ages. Genetic fate-mapping revealed that these Atoh1-expressing cells give rise solely to Merkel cells. Furthermore, selective ablation of Atoh1(+) skin cells in adult mice led to a permanent reduction in Merkel cell numbers, demonstrating that other stem cell populations are incapable of producing Merkel cells. These data identify a novel, unipotent progenitor population in the skin that gives rise to Merkel cells both during development and adulthood. © 2015 Wright et al.
PMID 25624394
http://jcb.rupress.org/content/208/3/367.long
2014
Merkel cells and touch domes: more than mechanosensory functions?
Exp Dermatol. 2014 Oct;23(10):692-5. doi: 10.1111/exd.12456. Epub 2014 Jul 16.
Xiao Y1, Williams JS, Brownell I.
Abstract
The touch dome (TD) is an innervated structure in the epidermis of mammalian skin. Composed of specialized keratinocytes and neuroendocrine Merkel cells, the TD has distinct molecular characteristics compared to the surrounding epidermal keratinocytes. Much of the research on Merkel cell function has focused on their role in mechanosensation, specifically light touch. Recently, more has been discovered about Merkel cell molecular characteristics and their cells of origin. Here we review Merkel cell and TD biology, and discuss potential functions beyond mechanosensation.
Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
KEYWORDS: Merkel cell; endocrine; immune; mechanosensation; touch dome
PMID 24862916 PMCID: PMC4180785 DOI: 10.1111/exd.12456
The gentle touch receptors of mammalian skin
Science. 2014 Nov 21;346(6212):950-4. doi: 10.1126/science.1254229.
Zimmerman A1, Bai L2, Ginty DD3.
Abstract
The skin is our largest sensory organ, transmitting pain, temperature, itch, and touch information to the central nervous system. Touch sensations are conveyed by distinct combinations of mechanosensory end organs and the low-threshold mechanoreceptors (LTMRs) that innervate them. Here we explore the various structures underlying the diverse functions of cutaneous LTMR end organs. Beyond anchoring of LTMRs to the surrounding dermis and epidermis, recent evidence suggests that the non-neuronal components of end organs play an active role in signaling to LTMRs and may physically gate force-sensitive channels in these receptors. Combined with LTMR intrinsic properties, the balance of these factors comprises the response properties of mechanosensory neurons and, thus, the neural encoding of touch. Copyright © 2014, American Association for the Advancement of Science.
PMID 25414303
Embryonic maturation of epidermal Merkel cells is controlled by a redundant transcription factor network
Development. 2014 Dec 15;141(24):4690-6. doi: 10.1242/dev.112169.
Perdigoto CN1, Bardot ES1, Valdes VJ1, Santoriello FJ1, Ezhkova E2.
Abstract
Merkel cell-neurite complexes are located in touch-sensitive areas of the mammalian skin and are involved in recognition of the texture and shape of objects. Merkel cells are essential for these tactile discriminations, as they generate action potentials in response to touch stimuli and induce the firing of innervating afferent nerves. It has been shown that Merkel cells originate from epidermal stem cells, but the cellular and molecular mechanisms of their development are largely unknown. In this study, we analyzed Merkel cell differentiation during development and found that it is a temporally regulated maturation process characterized by a sequential activation of Merkel cell-specific genes. We uncovered key transcription factors controlling this process and showed that the transcription factor Atoh1 is required for initial Merkel cell specification. The subsequent maturation steps of Merkel cell differentiation are controlled by cooperative function of the transcription factors Sox2 and Isl1, which physically interact and work to sustain Atoh1 expression. These findings reveal the presence of a robust transcriptional network required to produce functional Merkel cells that are required for tactile discrimination. © 2014. Published by The Company of Biologists Ltd. KEYWORDS: Merkel cells; Mouse; Skin; Stem cells
PMID 25468937
2012
Wetness perception across body sites
Neurosci Lett. 2012 Jul 26;522(1):73-7. Epub 2012 Jun 16.
Ackerley R, Olausson H, Wessberg J, McGlone F. Source Department of Physiology, University of Gothenburg, Box 432, Göteborg SE-40530, Sweden.
Abstract
Human skin is innervated with a variety of receptors serving somatosensation and includes the sensory sub-modalities of touch, temperature, pain and itch. The density and type of receptors differ across the body surface, and there are various body-map representations in the brain. The perceptions of skin sensations outside of the specified sub-modalities, e.g. wetness or greasiness, are described as 'touch blends' and are learned. The perception of wetness is generated from the coincident activation of tactile and thermal receptors. The present study aims to quantify threshold levels of wetness perception and find out if this differs across body sites. A rotary tactile stimulator was used to apply a moving, wetted stimulus over selected body sites at a precise force and velocity. Four wetness levels were tested over eight body sites. After each stimulus, the participant rated how wet the stimulus was perceived to be using a visual analogue scale. The results indicated that participants discriminated between levels of wetness as distinct percepts. Significant differences were found between all levels of wetness, apart from the lowest levels of comparison (20μl and 40μl). The perception of wetness did not, however, differ significantly across body sites and there were no significant interactions between wetness level and body site. The present study emphasizes the importance of understanding how bottom-up and top-down processes interact to generate complex perceptions. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
PMID 22710006
2011
Neuronal sensitivity of the skin
Eur J Dermatol. 2011 May;21 Suppl 2:43-7. Schmelz M. Source Department of Anesthesiology Mannheim, University Heidelberg, Mannheim. martin.schmelz@medma.uniheidelberg.de Abstract The skin is equipped with nerve fibers subserving the senses for touch, temperature, pain and itch. Thickly myelinated Aβ-fibers are linked to low threshold mechano-receptors responsible to detect vibration and slight indentation of the skin. Among the thinly myelinated Aδ-fibers one class is crucial for the cold detection, but there also nociceptive Aδ-fibers for the detection fast rising noxious heat and punctate mechanical stimuli. Unmyelinated C-fibers consist of various classes mediating nociceptive (pain and itch) and non-nociceptive (warmth, pleasant touch) sensations. The unmyelinated C-fibers have close contact to the keratinocytes and the interaction between C-fibers and local skin cells is of particular interest, as efferent neuronal function has both local trophic and immunomodulatory function. In turn, excitability of C-fibers is governed in part by neurotrophins from neighbouring skin cells such as keratinocytes. This mechanism is held responsible to induce and maintain chronic itch and pain conditions. Beyond this interaction recently a direct involvement of keratinocytes in the transduction process has been discussed especially for temperature and noxious stimuli, as keratinocytes express a variety of sensory transduction molecules. Thus, the interplay between neurons and non-neuronal cells is operational not only in basic physiology, but also in chronic itch and pain patients.
PMID 21628129
http://www.jle.com/en/revues/medecine/ejd/e-docs/00/04/67/62/article.phtml
A Shift in Sensory Processing that Enables the Developing Human Brain to Discriminate Touch from Pain
Curr Biol. 2011 Sep 7.
Fabrizi L, Slater R, Worley A, Meek J, Boyd S, Olhede S, Fitzgerald M. Source Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK. Abstract When and how infants begin to discriminate noxious from innocuous stimuli is a fundamental question in neuroscience [1]. However, little is known about the development of the necessary cortical somatosensory functional prerequisites in the intact human brain. Recent studies of developing brain networks have emphasized the importance of transient spontaneous and evoked neuronal bursting activity in the formation of functional circuits [2, 3]. These neuronal bursts are present during development and precede the onset of sensory functions [4, 5]. Their disappearance and the emergence of more adult-like activity are therefore thought to signal the maturation of functional brain circuitry [2, 4]. Here we show the changing patterns of neuronal activity that underlie the onset of nociception and touch discrimination in the preterm infant. We have conducted noninvasive electroencephalogram (EEG) recording of the brain neuronal activity in response to time-locked touches and clinically essential noxious lances of the heel in infants aged 28-45 weeks gestation. We show a transition in brain response following tactile and noxious stimulation from nonspecific, evenly dispersed neuronal bursts to modality-specific, localized, evoked potentials. The results suggest that specific neural circuits necessary for discrimination between touch and nociception emerge from 35-37 weeks gestation in the human brain.
Copyright © 2011 Elsevier Ltd. All rights reserved.
PMID 21906948
2010
Identification of epidermal progenitors for the Merkel cell lineage
Development. 2010 Dec;137(23):3965-71. Epub 2010 Nov 1.
Woo SH, Stumpfova M, Jensen UB, Lumpkin EA, Owens DM. Source Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. Abstract Epithelial stem cells in adult mammalian skin are known to maintain epidermal, follicular and sebaceous lineages during homeostasis. Recently, Merkel cell mechanoreceptors were identified as a fourth lineage derived from the proliferative layer of murine skin epithelium; however, the location of the stem or progenitor population for Merkel cells remains unknown. Here, we have identified a previously undescribed population of epidermal progenitors that reside in the touch domes of hairy skin, termed touch dome progenitor cells (TDPCs). TDPCs are epithelial keratinocytes and are distinguished by their unique co-expression of α6 integrin, Sca1 and CD200 surface proteins. TDPCs exhibit bipotent progenitor behavior as they give rise to both squamous and neuroendocrine epidermal lineages, whereas the remainder of the α6(+) Sca1(+) CD200(-) epidermis does not give rise to Merkel cells. Finally, TDPCs possess a unique transcript profile that appears to be enforced by the juxtaposition of TDPCs with Merkel cells within the touch dome niche.
PMID 21041368
2009
Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis
J Cell Biol. 2009 Oct 5;187(1):91-100. Epub 2009 Sep 28.
Van Keymeulen A, Mascre G, Youseff KK, Harel I, Michaux C, De Geest N, Szpalski C, Achouri Y, Bloch W, Hassan BA, Blanpain C.
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels B-1070, Belgium.
Abstract
Merkel cells (MCs) are located in the touch-sensitive area of the epidermis and mediate mechanotransduction in the skin. Whether MCs originate from embryonic epidermal or neural crest progenitors has been a matter of intense controversy since their discovery >130 yr ago. In addition, how MCs are maintained during adulthood is currently unknown. In this study, using lineage-tracing experiments, we show that MCs arise through the differentiation of epidermal progenitors during embryonic development. In adults, MCs undergo slow turnover and are replaced by cells originating from epidermal stem cells, not through the proliferation of differentiated MCs. Conditional deletion of the Atoh1/Math1 transcription factor in epidermal progenitors results in the absence of MCs in all body locations, including the whisker region. Our study demonstrates that MCs arise from the epidermis by an Atoh1-dependent mechanism and opens new avenues for study of MC functions in sensory perception, neuroendocrine signaling, and MC carcinoma.
PMID 19786578
2005
Human Merkel cells- aspects of cell biology, distribution and functions
Eur J Cell Biol. 2005 Mar;84(2-3):259-71.
Moll I1, Roessler M, Brandner JM, Eispert AC, Houdek P, Moll R.
Abstract
Human Merkel cells were first described by Friedrich S. Merkel in 1875 and named "Tastzellen" (touch cells) assuming a sensory touch function within the skin. Only ultrastructural research revealed their characteristics such as dense-core granules, plasma membrane spines and dendrites as well as a loosely arranged cytoskeleton. Biochemical analysis identified the expression of very specific cytokeratins (most notably CK 20) allowing the immunohistochemical detection of Merkel cells. In humans, they occur within the basal epidermis, being concentrated in eccrine glandular ridges of glabrous skin and in Haarscheiben of hairy skin, within belt-like clusters of hair follicles, and in certain mucosal tissues. Within the human skin, the dense-core granules contain heterogeneously distributed neuropeptides, some of which might work as neurotransmitters through which Merkel cells and their associated nerves exert their classical function as slowly adapting mechanoreceptors type I. This is the case in the Haarscheiben, small sensory organs containing keratinocytes with a special program of differentiation that includes the expression of CK 17 and Ber-EP4. Other peptides may act as growth factors and thus might participate in growth, differentiation and homeostasis of cutaneous structures. It is not yet clear whether the Merkel cell carcinomas, aggressive skin carcinomas, indeed arise from Merkel cells. We summarize and discuss data on the distribution, function and heterogeneity of human Merkel cells in normal and diseased skin. PMID: 15819406 DOI: 10.1016/j.ejcb.2004.12.023
2004
Pacinian corpuscle development involves multiple Trk signaling pathways
Dev Dyn. 2004 Nov;231(3):551-63.
Sedý J, Szeder V, Walro JM, Ren ZG, Nanka O, Tessarollo L, Sieber-Blum M, Grim M, Kucera J. Source Institute of Anatomy, Charles University, First Faculty of Medicine, U nemocnice 3, 128-00 Prague, Czech Republic. Abstract The development of crural Pacinian corpuscles was explored in neonatal mutant mice lacking nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) or neurotrophin-4 (NT4), or their cognate Trk receptors. Deficits of the corpuscles and their afferents were greatest in NT3, less in BDNF, and least in NT4 null mice. Deletion of NGF or p75(NTR) genes had little or no impact. No Pacinian corpuscles were present in NT3;BDNF and NT3;NT4 double or NT3;BDNF;NT4 triple null mice. Deficits were larger in NT3 than TrkC mutants and were comparable to deficits observed in TrkB or TrkA mutants. Afferents of all corpuscles coexpressed TrkA and TrkB receptors, and some afferents coexpressed all three Trk receptors. Our results suggest that multiple neurotrophins, in particular NT3, regulate the density of crural Pacinian corpuscles, most likely by regulating the survival of sensory neurons. In addition, NT3/TrkB and/or NT3/TrkA signaling plays a greater role than NT3/TrkC signaling in afferents to developing Pacinian corpuscles. (c) 2004 Wiley-Liss, Inc.
PMID 15376326
Mouse (129/Balb/c)
- crural Pacinian corpuscles took place over a 3-day period between embryonic day (E) 16.5 and postnatal day (P) 0 (with the delivery occurring on day E19)
- NT3 is the principal neurotrophin responsible for the development of afferents to Pacinian corpuscles
http://onlinelibrary.wiley.com/doi/10.1002/dvdy.20156/full
1990
The development of Meissner corpuscles in primate digital skin
Brain Res Dev Brain Res. 1990 Jan 1;51(1):35-44.
Renehan WE1, Munger BL.
Abstract
Digital skin from fetal and neonatal primates was examined using light and electron microscopic techniques to document the development of the Meissner corpuscle. Generation of the receptor was initiated early in the third trimester by fine neurites which left the superficial dermal nerve plexus, ascended the dermal papillae and entered the basal epidermis. As maturation of the Meissner corpuscle continued, the axons were confined to the apex of the dermal papilla, where they were oriented parallel to the surface to the surface of the skin and terminated among cytoplasmic extensions of presumptive lamellar cells. During late fetal life the complexity of the lamellar cell stacking increased and the lamellar cell bodies were found solely at the base of the receptor. Numerous axon terminals were evident between the cytoplasmic lamellae. The appearance of the neonatal Meissner corpuscle was indistinguishable from that of the adult, indicating that the complete cycle of development is concluded before birth.
PMID 2297894
