scholarly journals The cellular basis of mechanosensory Merkel-cell innervation during development

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Blair A Jenkins ◽  
Natalia M Fontecilla ◽  
Catherine P Lu ◽  
Elaine Fuchs ◽  
Ellen A Lumpkin
Keyword(s):  
Cell Types ◽  
Hair Follicles ◽  
Bmp Signaling ◽  
Merkel Cells ◽  
Merkel Cell ◽  
Skin Development ◽  
Cellular Basis ◽  
Neuronal Populations ◽  
Dermal Cells ◽  
Touch Dome

Touch sensation is initiated by mechanosensory neurons that innervate distinct skin structures; however, little is known about how these neurons are patterned during mammalian skin development. We explored the cellular basis of touch-receptor patterning in mouse touch domes, which contain mechanosensory Merkel cell-neurite complexes and abut primary hair follicles. At embryonic stage 16.5 (E16.5), touch domes emerge as patches of Merkel cells and keratinocytes clustered with a previously unsuspected population of Bmp4-expressing dermal cells. Epidermal Noggin overexpression at E14.5 disrupted touch-dome formation but not hair-follicle specification, demonstrating a temporally distinct requirement for BMP signaling in placode-derived structures. Surprisingly, two neuronal populations preferentially targeted touch domes during development but only one persisted in mature touch domes. Finally, Keratin-17-expressing keratinocytes but not Merkel cells were necessary to establish innervation patterns during development. These findings identify key cell types and signaling pathways required for targeting Merkel-cell afferents to discrete mechanosensory compartments.

scholarly journals Markel Cell Carcinoma

2010 ◽  
Vol 49 (178) ◽  
Author(s):  
S Wallis ◽  
A Durham-hall ◽  
N Tondon ◽  
TM Brotherstone ◽  
BM Shrestha
Keyword(s):  
Cell Carcinoma ◽  
Neuroendocrine Tumour ◽  
Basal Layer ◽  
Metastatic Potential ◽  
Hair Follicles ◽  
High Rate ◽  
Merkel Cells ◽  
Merkel Cell ◽  
Review Of The Literature ◽  
Poor Outcomes

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine tumour of the skin with high rate of local recurrence and distant metastatic potential leading to poor outcomes. Merkel cells are normally found as innervated clusters of cells around hair follicles in the basal layer of the epidermis and are thought to function as touch receptors. Here, we describe a case of MCC in a 71-year-old female and provide an up-to-date review of the literature pertinent to the management of MCC. KEYWORDS: merkell cell carcinoma, diagnosis, imunohistochemistry, management.

Localization of Merkel cells at hairless and hairy human skin sites using keratin 18

1995 ◽  
Vol 73 (9-10) ◽  
pp. 635-639 ◽  
Author(s):  
Julie Fradette ◽  
Marie-Josée Godbout ◽  
Martine Michel ◽  
Lucie Germain
Keyword(s):  
Human Skin ◽  
Basal Layer ◽  
Sensory Nerve ◽  
Neurosecretory Cells ◽  
Nerve Fibers ◽  
Hair Follicles ◽  
Merkel Cells ◽  
Merkel Cell ◽  
Skin Receptor ◽  
And Function

Merkel cells are neurosecretory cells of the skin with epithelial features such as desmosomes and expression of keratins 8, 18, 19, and 20. Merkel cells are scarcely distributed in adult human skin. Although they are present in hair follicles, their density is higher at hairless anatomic sites such as palms and soles. These cells are often innervated by sensory nerve fibers and are thought to be specialized mechanosensory skin receptor cells. However, their precise origin and function are not clearly established. The aim of this study was to localize Merkel cells in human hairless and hairy skin by immunohistochemistry with antibodies Ks18.174 and Ks19.1 directed against keratins 18 and 19, respectively. In glabrous skin of palm and sole, Merkel cells have been localized at the bottom of the rete ridges, in the epidermal basal layer. To study Merkel cell distribution at hairy anatomic sites, we have chosen breast skin, a tissue containing small hair follicles typical of those covering most of the body's surface. Merkel cells were present in the interfollicular epidermis. In hair follicles, they have been identified in the isthmus region.Key words: skin, human, Merkel cell, keratin, hair follicle.

scholarly journals Mouse notch: expression in hair follicles correlates with cell fate determination.

1993 ◽  
Vol 121 (3) ◽  
pp. 631-641 ◽  
Author(s):  
R Kopan ◽  
H Weintraub
Keyword(s):  
Hair Follicle ◽  
Cell Fate ◽  
Dermal Papilla ◽  
Cell Types ◽  
Cell Interaction ◽  
Hair Follicles ◽  
Skin Development ◽  
High Level ◽  
Cell Cell

Many vertebrate tissues, including skin, are known to develop as a consequence of epithelial-mesenchymal interactions. Much less is known about the role of cell-cell interaction within the epithelial or the mesenchymal compartments in morphogenesis. To investigate cell-cell interactions during skin development, and the potential role of the Notch homolog in this process, we cloned the mouse homolog of Notch (mNotch) and studied its expression pattern, starting as early as mesoderm formation. The novel application of double-labeled in situ hybridization in vertebrates allowed high resolution analysis to follow the fate of mNotch expressing cells directly. In comparison with the distribution of Id mRNA, analysis confirmed that in the hair follicle high levels of mNotch are expressed exclusively in the epithelial compartment. Hair follicle matrix cells start expressing mNotch as different cell types become distinguishable in the developing follicle. mNotch mRNA expression persists throughout the growth phase of the follicle and maintains the same expression profile in the second hair cycle. The cells in the follicle that undergo a phase of high level mNotch expression are in transition from mitotic precursors to several discreet, differentiating cell types. Our observations point out that both in time (during development) and in space (by being removed one cell layer from the dermal papilla) mNotch expression is clearly separated from the inductive interactions. This is a novel finding and suggests that mNotch is important for follicular differentiation and possibly cell fate selection within the follicle.

scholarly journals Homo- and heterotypic cell-cell contacts in Merkel cells and Merkel cell carcinomas: heterogeneity and indications for cadherin switching

2011 ◽  
Vol 58 (2) ◽  
pp. 286-303 ◽  
Author(s):  
Anna M Werling ◽  
Yvette Doerflinger ◽  
Johanna M Brandner ◽  
Franca Fuchs ◽  
Jürgen C Becker ◽  
...  
Keyword(s):  
Merkel Cells ◽  
Merkel Cell ◽  
Cell Contacts ◽  
Cell Cell

Metastasis of cancer from Merkel cells to the thyroid gland

2021 ◽  
Vol 19 (1) ◽  
pp. 86-88
Author(s):  
Piotr Przyczyna ◽  
◽  
Elżbieta Trojnar ◽  
Dorota Bartusik-Aebisher ◽  
David Aebisher ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Thyroid Cancer ◽  
Thyroid Gland ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Uterine Fibroids ◽  
Degenerative Changes ◽  
Merkel Cells ◽  
Merkel Cell ◽  
Left Buttock

Introduction. Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer. Aim. Herein described is a case of hypertensive patient, after removal of Merkel cancer of the left gluteus skin (2011), after pulmonary embolism (2013), with degenerative changes of the spine and uterine myoma, chronically treated with Warfarin, because of suspected thyroid cancer. Description of the case. A 70-year-old woman case after removing Merkel cancer of the left buttock skin (2011), after pulmonary embolism (2013), with degenerative changes of the spine and uterine fibroids treated chronically with Warfarin because of suspected thyroid cancer is described. Conclusion. Increasing evidence of Merkel cell carcinoma with immunodeficiency and neoplasia, and the management and outcome of these patients requires study.

scholarly journals NG2 Proteoglycan Expression in Mouse Skin: Altered Postnatal Skin Development in the NG2 Null Mouse

2007 ◽  
Vol 56 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Kuniko Kadoya ◽  
Jun-ichi Fukushi ◽  
Yoshihiro Matsumoto ◽  
Yu Yamaguchi ◽  
William B. Stallcup
Keyword(s):  
Stem Cell ◽  
Mouse Skin ◽  
Hair Follicles ◽  
Stem Cell Population ◽  
Null Mouse ◽  
Outer Root Sheath ◽  
Skin Development ◽  
Bulge Region ◽  
Ng2 Proteoglycan ◽  
Stem Cell Populations

In early postnatal mouse skin, the NG2 proteoglycan is expressed in the subcutis, the dermis, the outer root sheath of hair follicles, and the basal keratinocyte layer of the epidermis. With further development, NG2 is most prominently expressed by stem cells in the hair follicle bulge region, as also observed in adult human skin. During telogen and anagen phases of the adult hair cycle, NG2 is also found in stem cell populations that reside in dermal papillae and the outer root sheaths of hair follicles. Ablation of NG2 produces alterations in both the epidermis and subcutis layers of neonatal skin. Compared with wild type, the NG2 null epidermis does not achieve its full thickness due to reduced proliferation of basal keratinocytes that serve as the stem cell population in this layer. Thickening of the subcutis is also delayed in NG2 null skin due to deficiencies in the adipocyte population.

scholarly journals Single-cell analysis reveals cellular heterogeneity and molecular determinants of hypothalamic leptin-receptor cells

2020 ◽  
Author(s):  
N. Kakava-Georgiadou ◽  
J.F. Severens ◽  
A.M. Jørgensen ◽  
K.M. Garner ◽  
M.C.M Luijendijk ◽  
...  
Keyword(s):  
Single Cell ◽  
Leptin Receptor ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Molecular Signature ◽  
Neuronal Populations ◽  
Hypothalamic Nuclei ◽  
Satiety Hormone ◽  
Multiple Cell

AbstractHypothalamic nuclei which regulate homeostatic functions express leptin receptor (LepR), the primary target of the satiety hormone leptin. Single-cell RNA sequencing (scRNA-seq) has facilitated the discovery of a variety of hypothalamic cell types. However, low abundance of LepR transcripts prevented further characterization of LepR cells. Therefore, we perform scRNA-seq on isolated LepR cells and identify eight neuronal clusters, including three uncharacterized Trh-expressing populations as well as 17 non-neuronal populations including tanycytes, oligodendrocytes and endothelial cells. Food restriction had a major impact on Agrp neurons and changed the expression of obesity-associated genes. Multiple cell clusters were enriched for GWAS signals of obesity. We further explored changes in the gene regulatory landscape of LepR cell types. We thus reveal the molecular signature of distinct populations with diverse neurochemical profiles, which will aid efforts to illuminate the multi-functional nature of leptin’s action in the hypothalamus.

scholarly journals Single cell transcriptome profiling of the human developing spinal cord reveals a conserved genetic programme with human specific features

2021 ◽  
Author(s):  
Teresa Rayon ◽  
Rory J. Maizels ◽  
Christopher Barrington ◽  
James Briscoe
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Single Cell ◽  
Motor Neurons ◽  
Neural Tube ◽  
Transcriptome Profiling ◽  
Cell Types ◽  
Human Embryos ◽  
Neuronal Populations ◽  
Cell Transcriptome

AbstractThe spinal cord receives input from peripheral sensory neurons and controls motor output by regulating muscle innervating motor neurons. These functions are carried out by neural circuits comprising molecularly and physiologically distinct neuronal subtypes that are generated in a characteristic spatial-temporal arrangement from progenitors in the embryonic neural tube. The systematic mapping of gene expression in mouse embryos has provided insight into the diversity and complexity of cells in the neural tube. For human embryos, however, less information has been available. To address this, we used single cell mRNA sequencing to profile cervical and thoracic regions in four human embryos of Carnegie Stages (CS) CS12, CS14, CS17 and CS19 from Gestational Weeks (W) 4-7. In total we recovered the transcriptomes of 71,219 cells. Analysis of progenitor and neuronal populations from the neural tube, as well as cells of the peripheral nervous system, in dorsal root ganglia adjacent to the neural tube, identified dozens of distinct cell types and facilitated the reconstruction of the differentiation pathways of specific neuronal subtypes. Comparison with existing mouse datasets revealed the overall similarity of mouse and human neural tube development while highlighting specific features that differed between species. These data provide a catalogue of gene expression and cell type identity in the developing neural tube that will support future studies of sensory and motor control systems and can be explored at https://shiny.crick.ac.uk/scviewer/neuraltube/.

scholarly journals Pathway-dependent regulation of sleep dynamics in a network model of the sleep-wake cycle

2019 ◽  
Author(s):  
Charlotte Héricé ◽  
Shuzo Sakata
Keyword(s):  
Computational Model ◽  
Eye Movement ◽  
Network Model ◽  
Rem Sleep ◽  
Synaptic Weight ◽  
Nrem Sleep ◽  
Cell Types ◽  
Brain Areas ◽  
Neuronal Populations ◽  
Neural Populations

AbstractSleep is a fundamental homeostatic process within the animal kingdom. Although various brain areas and cell types are involved in the regulation of the sleep-wake cycle, it is still unclear how different pathways between neural populations contribute to its regulation. Here we address this issue by investigating the behavior of a simplified network model upon synaptic weight manipulations. Our model consists of three neural populations connected by excitatory and inhibitory synapses. Activity in each population is described by a firing-rate model, which determines the state of the network. Namely wakefulness, rapid eye movement (REM) sleep or non-REM (NREM) sleep. By systematically manipulating the synaptic weight of every pathway, we show that even this simplified model exhibits non-trivial behaviors: for example, the wake-promoting population contributes not just to the induction and maintenance of wakefulness, but also to sleep induction. Although a recurrent excitatory connection of the REM-promoting population is essential for REM sleep genesis, this recurrent connection does not necessarily contribute to the maintenance of REM sleep. The duration of NREM sleep can be shortened or extended by changes in the synaptic strength of the pathways from the NREM-promoting population. In some cases, there is an optimal range of synaptic strengths that affect a particular state, implying that the amount of manipulations, not just direction (i.e., activation or inactivation), needs to be taken into account. These results demonstrate pathway-dependent regulation of sleep dynamics and highlight the importance of systems-level quantitative approaches for sleep-wake regulatory circuits.Author SummarySleep is essential and ubiquitous across animal species. Over the past half-century, various brain areas, cell types, neurotransmitters, and neuropeptides have been identified as part of a sleep-wake regulating circuitry in the brain. However, it is less explored how individual neural pathways contribute to the sleep-wake cycle. In the present study, we investigate the behavior of a computational model by altering the strength of connections between neuronal populations. This computational model is comprised of a simple network where three neuronal populations are connected together, and the activity of each population determines the current state of the model, that is, wakefulness, rapid-eye-movement (REM) sleep or non-REM (NREM) sleep. When we alter the connection strength of each pathway, we observe that the effect of such alterations on the sleep-wake cycle is highly pathway-dependent. Our results provide further insights into the mechanisms of sleep-wake regulation, and our computational approach can complement future biological experiments.

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