An airway-to-brain sensory pathway mediates influenza-induced sickness.

Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes. On infection, immune cells release a 'storm' of cytokines and other mediators, many of which are detected by neurons; yet, the responding neural circuits and neuro-immune interaction mechanisms that evoke sickness behaviour during naturalistic infections remain unclear. Over-the-counter medications such as aspirin and ibuprofen are widely used to alleviate sickness and act by blocking prostaglandin E2 (PGE2) synthesis.

Internal senses of the vagus nerve.

The vagus nerve is an indispensable body-brain connection that controls vital aspects of autonomic physiology like breathing, heart rate, blood pressure, and gut motility, reflexes like coughing and swallowing, and survival behaviors like feeding, drinking, and sickness responses. Classical physiological studies and recent molecular/genetic approaches have revealed a tremendous diversity of vagal sensory neuron types that innervate different internal organs, with many cell types remaining poorly understood. Here, we review the state of knowledge related to vagal sensory neurons that innervate the respiratory, cardiovascular, and digestive systems.

Area Postrema Cell Types that Mediate Nausea-Associated Behaviors.

Nausea, the unpleasant sensation of visceral malaise, remains a mysterious process. The area postrema is implicated in some nausea responses and is anatomically privileged to detect blood-borne signals. To investigate nausea mechanisms, we built an area postrema cell atlas through single-nucleus RNA sequencing, revealing a few neuron types.

An Airway Protection Program Revealed by Sweeping Genetic Control of Vagal Afferents.

Sensory neurons initiate defensive reflexes that ensure airway integrity. Dysfunction of laryngeal neurons is life-threatening, causing pulmonary aspiration, dysphagia, and choking, yet relevant sensory pathways remain poorly understood. Here, we discover rare throat-innervating neurons (∼100 neurons/mouse) that guard the airways against assault.

Arterial Baroreceptors Sense Blood Pressure through Decorated Aortic Claws.

Mechanosensory neurons across physiological systems sense force using diverse terminal morphologies. Arterial baroreceptors are sensory neurons that monitor blood pressure for real-time stabilization of cardiovascular output. Various aortic sensory terminals have been described, but those that sense blood pressure are unclear because of a lack of selective genetic tools.

Ever-Changing Landscapes: Transcriptional Enhancers in Development and Evolution.

A class of cis-regulatory elements, called enhancers, play a central role in orchestrating spatiotemporally precise gene-expression programs during development. Consequently, divergence in enhancer sequence and activity is thought to be an important mediator of inter- and intra-species phenotypic variation. Here, we give an overview of emerging principles of enhancer function, current models of enhancer architecture, genomic substrates from which enhancers emerge during evolution, and the influence of three-dimensional genome organization on long-range gene regulation.

Enhancer divergence and cis-regulatory evolution in the human and chimp neural crest.

cis-regulatory changes play a central role in morphological divergence, yet the regulatory principles underlying emergence of human traits remain poorly understood. Here, we use epigenomic profiling from human and chimpanzee cranial neural crest cells to systematically and quantitatively annotate divergence of craniofacial cis-regulatory landscapes. Epigenomic divergence is often attributable to genetic variation within TF motifs at orthologous enhancers, with a novel motif being most predictive of activity biases.

Human genetic variation within neural crest enhancers: molecular and phenotypic implications.

Developmental gene expression programmes are coordinated by the specialized distal cis-regulatory elements called enhancers, which integrate lineage- and signalling-dependent inputs to guide morphogenesis. In previous work, we characterized the genome-wide repertoire of active enhancers in human neural crest cells (hNCC), an embryonic cell population with critical roles in craniofacial development. We showed that in hNCC, co-occupancy of a master regulator TFAP2A with nuclear receptors NR2F1 and NR2F2 correlates with the presence of permissive enhancer chromatin states.

Alternative polyadenylation mediates microRNA regulation of muscle stem cell function.

Pax3, a key myogenic regulator, is transiently expressed during activation of adult muscle stem cells, or satellite cells (SCs), and is also expressed in a subset of quiescent SCs (QSCs), but only in specific muscles. The mechanisms regulating these variations in expression are not well understood. Here we show that Pax3 levels are regulated by miR-206, a miRNA with a previously demonstrated role in myogenic differentiation.