Merkel Cell-Driven BDNF Signaling Specifies SAI Neuron Molecular and Electrophysiological Phenotypes

Reed-Geaghan, Erin G.; Wright, Margaret C.; See, Lauren; Adelman, Peter; Lee, Kuan Hsien; Koerber, H. Richard; Maricich, Stephen M.

doi:10.1523/jneurosci.3781-15.2016

Cited by 18 publications

(16 citation statements)

References 65 publications

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“…However, Merkel cells of the glabrous skin did decrease between P0 and P21. We have noted that Merkel cells of the paw are generated later in development than Merkel cells of the back and belly skin (Reed-Geaghan et al, 2016), likely explaining this decrease in percentage of cells in early postnatal life. Consistent with a lack of new Merkel cell production in glabrous skin that we noted from chronic EdU exposure from 3–8 weeks of age, the percentage of EdU+ Merkel cells from P21 to 9 months of age is again unchanged.…”

Section: Discussionmentioning

confidence: 88%

Merkel cells are long-lived cells whose production is stimulated by skin injury

Wright

Logan

Bolock

et al. 2017

Developmental Biology

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Mechanosensitive Merkel cells are thought to have finite lifespans, but controversy surrounds the frequency of their replacement and which precursor cells maintain the population. We found by embryonic EdU administration that Merkel cells undergo terminal cell division in late embryogenesis and survive long into adulthood. We also found that new Merkel cells are produced infrequently during normal skin homeostasis and that their numbers do not change during natural or induced hair cycles. In contrast, live imaging and EdU experiments showed that mild mechanical injury produced by skin shaving dramatically increases Merkel cell production. We confirmed with genetic cell ablation and fate-mapping experiments that new touch dome Merkel cells in adult mice arise from touch dome keratinocytes. Together, these independent lines of evidence show that Merkel cells in adult mice are long-lived, are replaced rarely during normal adult skin homeostasis, and that their production can be induced by repeated shaving. These results have profound implications for understanding sensory neurobiology and human diseases such as Merkel cell carcinoma.

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Section: Discussionmentioning

confidence: 88%

Merkel cells are long-lived cells whose production is stimulated by skin injury

Wright

Logan

Bolock

et al. 2017

Developmental Biology

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“…The reduction of Merkel cells during anagen coincided with the loss of neurites in touch-dome afferents, raising the possibility that these cell types are interdependent. It is unlikely that loss of Merkel cells drives neuronal remodeling, as touch-dome innervation does not require intact Merkel cells (Maricich et al , 2009; Reed-Geaghan et al , 2016). By contrast, intact innervation and neural-derived signals are needed to maintain full complements of touch-dome Merkel cells (Nurse et al , 1984; Xiao et al , 2015).…”

Section: Discussionmentioning

confidence: 99%

Touch Receptors Undergo Rapid Remodeling in Healthy Skin

Marshall¹,

Clary²,

Baba³

et al. 2016

Cell Reports

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Summary Sensory tissues exposed to the environment, such as skin, olfactory epithelia and taste buds, continuously renew; therefore, peripheral neurons must have mechanisms to maintain appropriate innervation patterns. Although somatosensory neurons regenerate after injury, little is known about how these neurons cope with normal target-organ changes. To elucidate neuronal plasticity in healthy skin, we analyzed the structure of Merkel-cell afferents, which are gentle touch receptors, during skin remodeling that accompanies mouse hair-follicle regeneration. The number of Merkel cells is reduced by 90% and axonal arbors are simplified during active hair growth. These structures rebound within just days. Computational modeling predicts that Merkel-cell changes are probabilistic but myelinated branch stability depends on Merkel-cell inputs. Electrophysiology and behavior demonstrate that tactile responsiveness is less reliable during active growth than in resting skin. These results reveal that somatosensory neurons display structural plasticity at the cost of impairment in the reliability of encoding gentle touch.

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“…To directly test the contribution of Merkel cells in regulating alloknesis, we measured mechanical itch in Merkel cell–deficient K14 Cre ; Atoh1 f/f mice (4,14). These mice showed significantly increased scratching in response to mild von Frey filament stimulations when compared with Cre − littermate control mice (Fig.…”

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confidence: 99%

Piezo2 channel–Merkel cell signaling modulates the conversion of touch to itch

Feng¹,

Luo²,

Pu³

et al. 2018

Science

151

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The somatosensory system relays many signals ranging from light touch to pain and itch.Touch is critical to spatial awareness and communication. However, in disease states, innocuous mechanical stimuli can provoke pathologic sensations such as mechanical itch (alloknesis). The molecular and cellular mechanisms that govern this conversion remain unknown. We found that in mice, alloknesis in aging and dry skin is associated with a loss of Merkel cells, the touch receptors in the skin. Targeted genetic deletion of Merkel cells and associated mechanosensitive Piezo2 channels in the skin was sufficient to produce alloknesis. Chemogenetic activation of Merkel cells protected against alloknesis in dry skin. This study reveals a previously unknown function of the cutaneous touch receptors and may provide insight into the development of alloknesis.

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Merkel Cell-Driven BDNF Signaling Specifies SAI Neuron Molecular and Electrophysiological Phenotypes

Cited by 18 publications

References 65 publications

Merkel cells are long-lived cells whose production is stimulated by skin injury

Merkel cells are long-lived cells whose production is stimulated by skin injury

Touch Receptors Undergo Rapid Remodeling in Healthy Skin

Piezo2 channel–Merkel cell signaling modulates the conversion of touch to itch

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