Genetic Identification of an Expansive Mechanoreceptor Sensitive to Skin Stroking

Bai, Lijun; Lehnert, Brendan P.; Liu, Junwei; Neubarth, Nicole; Dickendesher, Travis L.; Nwe, Pann H.; Cassidy, Colleen; Woodbury, C. Jeffery; Ginty, David D.

doi:10.1016/j.cell.2015.11.060

Cited by 165 publications

(266 citation statements)

References 38 publications

(53 reference statements)

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“…Specimens were stained for markers of mature Merkel cells (Keratin 8; K8; Kim and Holbrook, 1995), myelinated afferents (Neurofilament H; NFH) and myelin (myelin basic protein; MBP; Lesniak et al , 2014). Merkel-cell afferents were identified based on morphology and juxtaposition to guard hair follicles (Iggo and Muir, 1969), which were recognized by their NFH-positive lanceolate endings (Bai et al , 2015; Li et al , 2011). Merkel-cell afferents, which branch to contact Merkel cells, can be distinguished from other NFH-positive afferents based on two additional anatomical features.…”

Section: Resultsmentioning

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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Section: Resultsmentioning

confidence: 99%

Touch Receptors Undergo Rapid Remodeling in Healthy Skin

Marshall¹,

Clary²,

Baba³

et al. 2016

Cell Reports

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“…Recent advances revealed neuron types involved in numerous perceptions and behaviors, such as touch, itch, hunger, and aggression (Aponte et al, 2011; Bai et al, 2015; Han et al, 2013; Lee et al, 2014). Genetic approaches help paint a comprehensive picture of neuron function that includes gene expression, peripheral anatomy, central anatomy, in vivo and in vitro responsiveness, and physiological function.…”

Section: Discussionmentioning

confidence: 99%

Sensory Neurons that Detect Stretch and Nutrients in the Digestive System

Williams

Chang

Strochlic

et al. 2016

Cell

474

513

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SUMMARY Neural inputs from internal organs are essential for normal autonomic function. The vagus nerve is a key body-brain connection that monitors the digestive, cardiovascular, and respiratory systems. Within the gastrointestinal tract, vagal sensory neurons detect gut hormones and organ distension. Here, we investigate the molecular diversity of vagal sensory neurons and their roles in sensing gastrointestinal inputs. Genetic approaches allowed targeted investigation of gut-to-brain afferents involved in homeostatic responses to ingested nutrients (GPR65 neurons) and mechanical distension of the stomach and intestine (GLP1R neurons). Optogenetics, in vivo ganglion imaging, and genetically guided anatomical mapping provide direct links between neuron identity, peripheral anatomy, central anatomy, conduction velocity, response properties in vitro and in vivo, and physiological function. These studies clarify the roles of vagal afferents in mediating particular gut hormone responses. Moreover, genetic control over gut-to-brain neurons provides a molecular framework for understanding neural control of gastrointestinal physiology.

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“…Sensory afferents have highly specialized endings that are likely important for mechanosensation (Bai et al, 2015; Rutlin et al, 2014). In mammals, other forms of mechanosensory specialization have been observed.…”

Section: Discussionmentioning

confidence: 99%

Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

et al. 2017

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Summary Piezo2 is a mechanically activated ion-channel required for touch discrimination, vibration detection and proprioception. Here we discovered that Piezo2 is extensively spliced, producing different Piezo2 isoforms with distinct properties. Sensory neurons from both mice and humans express a large repertoire of Piezo2 variants, while non-neuronal tissues express predominantly a single isoform. Notably, even within sensory ganglia, we demonstrate the splicing of Piezo2 to be cell-type specific. Biophysical characterization revealed substantial differences in ion-permeability, sensitivity to calcium modulation, and inactivation kinetics among Piezo2 splice variants. Together our results describe, at the molecular level, a potential mechanism by which transduction is tuned permitting the detection of a variety of mechanosensory stimuli.

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Genetic Identification of an Expansive Mechanoreceptor Sensitive to Skin Stroking

Cited by 165 publications

References 38 publications

Touch Receptors Undergo Rapid Remodeling in Healthy Skin

Touch Receptors Undergo Rapid Remodeling in Healthy Skin

Sensory Neurons that Detect Stretch and Nutrients in the Digestive System

Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

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