PIEZO2 in somatosensory neurons controls gastrointestinal transit

Servin‐Vences, M. Rocio; Lam, Ruby M.; Koolen, Alize; Wang, Yu; Saade, D.; Loud, Meaghan; Kacmaz, Halil; Frausto, Suzanne; Zhang, Yunxiao; Beyder, Arthur; Marshall, Kara L.; Bönnemann, Carsten G.; Chesler, Alexander T.; Patapoutian, Ardem

doi:10.1016/j.cell.2023.07.006

Cited by 39 publications

(18 citation statements)

References 86 publications

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“…Under experimental conditions, animals have demonstrated the ability to favor the activation of certain selective sympathetic outflows 6,7 . Sympathetic output specificity has also been suggested in recent research regarding the somatotopic nature of acupuncture 46 , the selective sympathetic impacts on the GI tract mediated by vagal sensing of gut microbiota 33 or gut mechanosensation 47 , and the top-down regulation of immune responses within delimited regions of the body 48 . However, the precise cellular underpinnings within SPNs for these distinctive sympathetic outflows remain largely unknown.…”

Section: Discussionmentioning

confidence: 95%

Parallel Labeled-Line Organization of Sympathetic Outflow for Selective Organ Regulation in Mice

Harima,

Tsurutani,

Uchida

et al. 2024

Preprint

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The sympathetic nervous system is vital in maintaining homeostasis and responding to environmental changes1–3. This regulation is coordinated by the spinal sympathetic preganglionic neurons (SPNs), which influence various organs both through neuronal pathways via postganglionic neurons and through endocrine processes by innervating the adrenal gland. Despite decades of research supporting the concept of selective control within this system1,4–9, the neural circuit organization responsible for the specificity of sympathetic outflow remains poorly understood. Notably, classical anatomical studies in rats have not revealed a definitive molecular code governing SPNs, nor have they confirmed the existence of SPNs strictly corresponding to specific output targets1,6,10,11. To reconcile this discrepancy, we aim to integrate recent transcriptome data of SPNs12,13in mice with viral-genetic toolkits14to map axonal projections and manipulate the functions of SPNs governing the gastrointestinal tract and adrenal gland. Here, we have identified two subtypes of SPNs in the lower thoracic spinal cord, defined at the molecular level, exhibiting non-overlapping patterns of innervation. Chemogenetic manipulations on these distinct SPN subtypes revealed selective impacts on the digestive functions in the gastrointestinal tracts or glucose metabolism mediated by the adrenal gland, respectively. This molecularly delineated parallel labeled-line organization in sympathetic outflows presents a potential avenue for selectively manipulating organ functions.

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Section: Discussionmentioning

confidence: 95%

Parallel Labeled-Line Organization of Sympathetic Outflow for Selective Organ Regulation in Mice

Harima,

Tsurutani,

Uchida

et al. 2024

Preprint

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“…Recent reports have found that extrinsic sensory innervation clearly exhibits mechano-and chemosensory roles in the small and large intestine 27,36,49,88,103,104,[116][117][118] . Our observations support an extension of this model in which select subclasses of enteric neurons can influence food consumption via the dorsal root ganglia.…”

Section: Interactions Between the Enteric Nervous System And Extrinsi...mentioning

confidence: 99%

“…Fecal events were continually monitored for six hours and plotted as a function of time. Fluid content of fecal matter was determined largely as previously described 118 . Briefly, freshly produced fecal samples were immediately removed from the petri dish and weighed to determine the total weight.…”

Section: Behavioral Measurementsmentioning

confidence: 99%

Differential control of intestine function by genetically defined enteric neurons

Shi,

Reddy,

Walker

et al. 2024

Preprint

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The function of the intestine is regulated by direct innervation from a combination of enteric, sensory, and autonomic neurons. A central question in neurobiology is how these distinct peripheral neuron populations collectively control intestinal function. However, disambiguating the functions of intestine-innervating neuronal populations has been a challenge. Using intersectional genetic approaches in mice, we enable precise manipulations of defined neuronal populations within the intestinal tract. We examined enteric neurons, which represent the majority of intestine-innervating neurons, by genetically isolating neuronal subclasses, identifying their morphological specializations, and defining subclass-specific influences on intestinal functions. We further found that food consumption can be modulated by select enteric neuron populations via the spinal sensory afferent pathway. Taken together, the presented molecular genetic characterization of intestine-innervating neurons establishes a foundation for detailed studies of the enteric nervous system and its interactions with the broader neural networks of the body.

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“…PIEZO1 is endogenously expressed in many tissue types including vascular endothelium and smooth muscle, and is important for vascular development and function 26,27 . PIEZO2 is mainly expressed in peripheral sensory neurons and specialized accessory sensory cells and is required for gentle touch sensation, proprioception, and gut and bladder function [28][29][30][31] . Together, PIEZO1 and PIEZO2 in vagal sensory neurons initiate the neuronal baroreflex through sensing of blood pressure in the aortic arch 5 .…”

Section: Piezo2 Is Expressed In Juxtaglomerular and Mesangial Cells O...mentioning

confidence: 99%

Renal mechanotransduction is an essential regulator of renin

Hill,

Shirvan,

Burquez

et al. 2023

Preprint

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The kidneys tightly control the composition of our internal environment to maintain homeostasis in the face of external variability. The regulation of blood volume begins in the kidneys and is essential for vertebrate life in terrestrial environments where salt and water availability are unpredictable1,2. Renin synthesis and release by juxtaglomerular granular cells of the kidney is the rate-limiting step in a hormonal cascade that modulates blood volume, filtration, and salt balance2. Renin is stimulated during hypovolemia and salt deprivation in response to chemical cues released from sympathetic efferent neurons and the macula densa onto the juxtaglomerular granular cells. Renin levels are also proposed to be modulated by mechanical forces elicited by changes in blood volume and/or pressure exerted upon juxtaglomerular cells2–4. However, the identity and significance of the juxtaglomerular mechanotransducer(s) was unknown. We found that the force-gated ion channel PIEZO2 is expressed in juxtaglomerular granular cells and in neighboring mesangial cells. Selective genetic ablation of PIEZO2 dysregulated the renin-angiotensin-aldosterone system by elevating renin, raising systemic blood pressure, inducing glomerular hyperfiltration, and exaggerating the hormonal response to volume depletion. These findings demonstrate that PIEZO2 contributes to renal blood volume sensing and kidney functionin vivo.

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PIEZO2 in somatosensory neurons controls gastrointestinal transit

Cited by 39 publications

References 86 publications

Parallel Labeled-Line Organization of Sympathetic Outflow for Selective Organ Regulation in Mice

Parallel Labeled-Line Organization of Sympathetic Outflow for Selective Organ Regulation in Mice

Differential control of intestine function by genetically defined enteric neurons

Renal mechanotransduction is an essential regulator of renin

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