Merkel Cells Activate Sensory Neural Pathways through Adrenergic Synapses

Hoffman, Benjamin U.; Baba, Yoshichika; Griffith, Theanne N.; Mosharov, Eugene V.; Woo, Seung-Hyun; Roybal, Daniel; Karsenty, G.; Patapoutian, Ardem; Sulzer, David; Lumpkin, Ellen A.

doi:10.1016/j.neuron.2018.10.034

Cited by 102 publications

(128 citation statements)

References 123 publications

(177 reference statements)

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“…We performed transcriptional profiling of Merkel cells isolated from back and glabrous paw skins of newborn mice and identified that these cells share similar transcriptomes. Consistent with previous studies, among commonly expressed genes were transcription factors Atoh1 and Sox2, which have been shown to be essential for Merkel cell formation in glabrous and back skin . In epidermal progenitors, Atoh1 and Sox2 are regulated by the epigenetic repressor PRC2.…”

Section: Discussionsupporting

confidence: 87%

Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2‐mediated signalling

Nguyen

Valdés

Cohen

et al. 2019

Experimental Dermatology

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Merkel cells are mechanosensory cells involved in tactile discrimination. Merkel cells have been primarily studied in the murine back skin, where they are found in specialized structures called touch domes located around primary hair follicles. Yet, little is known about the morphogenesis of Merkel cells in areas of the skin devoid of hair, such as the glabrous paw skin. Here, we describe Merkel cell formation in the glabrous paw skin during embryogenesis. We first found in the glabrous paw skin that Merkel cells were specified at E15.5, 24 hours later, compared to in the back skin. Additionally, by performing lineage‐tracing experiments, we found that unlike in the back skin, SOX9(+) cells do not give rise to Merkel cells in the glabrous paw skin. Finally, we compared the transcriptomes of Merkel cells in the back and the glabrous paw skin and showed that they are similar. Genetic and transcriptome studies showed that the formation of Merkel cells in both regions was controlled by similar regulators. Among them was FGFR2, an upstream factor of MAPK signalling that was reported to have a critical function in Merkel cell formation in the back skin. Here, we showed that FGFR2 is also required for Merkel cell development in the glabrous paw skin. Taken together, our results demonstrate that Merkel cells in the murine back skin and glabrous paw skin are similar, and even though their formation is controlled by a common genetic programme, their precursor cells might differ.

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Section: Discussionsupporting

confidence: 87%

Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2‐mediated signalling

Nguyen

Valdés

Cohen

et al. 2019

Experimental Dermatology

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“…RNAscope analysis was performed using the ACDbio RNAscope kit for nonfixed tissue (ACD #320851) as described previously (Hoffman et al, 2018). In short, DRG were dissected on ice and fixed for 15 min in 4% PFA.…”

Section: Methodsmentioning

confidence: 99%

“…To validate the subtype-selective expression of these transcripts more directly, we sought to perform colocalization studies with PV. Because immunological reagents for all but one of our markers (Pln) were either unavailable or unreliable, we largely performed these experiments using RNAscope technology (Hoffman et al, 2018). For most of these analyses, we assessed expression of our marker genes in PV neurons defined by PV transcript expression ( Fig.…”

Section: Newly Identified Psn-enriched Transcripts Mark Proprioceptormentioning

confidence: 99%

A Role for Sensory end Organ-Derived Signals in Regulating Muscle Spindle Proprioceptor Phenotype

Schieren

Qian

et al. 2019

J. Neurosci.

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Proprioceptive feedback from Group Ia/II muscle spindle afferents and Group Ib Golgi tendon afferents is critical for the normal execution of most motor tasks, yet how these distinct proprioceptor subtypes emerge during development remains poorly understood. Using molecular genetic approaches in mice of either sex, we identified 24 transcripts that have not previously been associated with a proprioceptor identity. Combinatorial expression analyses of these markers reveal at least three molecularly distinct proprioceptor subtypes. In addition, we find that 12 of these transcripts are expressed well after proprioceptors innervate their respective sensory receptors, and expression of three of these markers, including the heart development molecule Heg1, is significantly reduced in mice that lack muscle spindles. These data reveal Heg1 as a putative marker for proprioceptive muscle spindle afferents. Moreover, they suggest that the phenotypic specialization of functionally distinct proprioceptor subtypes depends, in part, on extrinsic sensory receptor organderived signals. Sensory feedback from muscle spindle (MS) and Golgi tendon organ (GTO) sensory end organs is critical for normal motor control, but how distinct MS and GTO afferent sensory neurons emerge during development remains poorly understood. Using (bulk)transcriptome analysis of genetically identified proprioceptors, this work reveals molecular markers for distinct proprioceptor subsets, including some that appear selectively expressed in MS afferents. Detailed analysis of the expression of these transcripts provides evidence that MS/GTO afferent subtype phenotypes may, at least in part, emerge through extrinsic, sensory end organderived signals.

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“…Patch‐clamp recordings showed that only 5‐HT but not other neurotransmitters (including ATP, Glu, NE) elicited SAI impulses in nerve bundles attached with whisker hair follicle . In marked contrast, another recent study demonstrated that NE but not 5‐HT or dopamine evoked action potentials in the SAI afferents in ex vivo skin‐nerve preparations . Thus, whether Merkel cell‐neurite complex is formed by serotonergic or adrenergic synapses needs further confirmation.…”

Section: Physiological Functions Of Merkel Discmentioning

confidence: 99%

A novel player in the field: Merkel disc in touch, itch and pain

Feng

2019

Experimental Dermatology

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The mechanosensitive Merkel cell‐neurite complex comprising two distinct cell types in both hairy and glabrous skin has been widely recognized as touch receptor for more than 100 years. In 2014, three elegant studies further demonstrated that the Merkel cell‐neurite complex mediates touch transduction via the mechanosensitive Piezo2 channel. However, whether it is involved in genesis of itch and pain sensations, has been unclear. Recently, we reported that Merkel cells modulate the development of mechanical itch under the conditions of dry skin and aging, whereas two other studies demonstrated that Piezo2 channel mediates mechanical pain. In this assay, we summarized the current knowledge of Merkel disk under both normal and pathological conditions, with a focus on its role in touch, itch, and pain.

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Merkel Cells Activate Sensory Neural Pathways through Adrenergic Synapses

Cited by 102 publications

References 123 publications

Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2‐mediated signalling

Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2‐mediated signalling

A Role for Sensory end Organ-Derived Signals in Regulating Muscle Spindle Proprioceptor Phenotype

A novel player in the field: Merkel disc in touch, itch and pain

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