Convergent cardiorespiratory neurons represent a significant portion of cardiac and respiratory neurons in the vagal ganglia.

Significant cardiorespiratory coordination is required to maintain physiological function in health and disease. Sensory neuronal "cross-talk" between the heart and the lungs is required for synchronous regulation of normal cardiopulmonary function and is most likely mediated by the convergence of sensory neural pathways present in the autonomic ganglia. Using neurotracer approaches with appropriate negative control experiments in a mouse model, presence of cardiorespiratory neurons in the vagal (nodose) ganglia are demonstrated.

A census of the lung: CellCards from LungMAP.

The human lung plays vital roles in respiration, host defense, and basic physiology. Recent technological advancements such as single-cell RNA sequencing and genetic lineage tracing have revealed novel cell types and enriched functional properties of existing cell types in lung. The time has come to take a new census.

Identification of lung innervating sensory neurons and their target specificity.

Known as the gas exchange organ, the lung is also critical for responding to the aerosol environment in part through interaction with the nervous system. The diversity and specificity of lung innervating neurons remain poorly understood. Here, we interrogated the cell body location and molecular signature and projection pattern of lung innervating sensory neurons.

Inactivation of Lats1 and Lats2 highlights the role of hippo pathway effector YAP in larynx and vocal fold epithelium morphogenesis.

Proliferation and differentiation of vocal fold epithelial cells during embryonic development is poorly understood. We examined the role of Hippo signaling, a vital pathway known for regulating organ size, in murine laryngeal development. Conditional inactivation of the Hippo kinase genes Lats1 and Lats2, specifically in vocal fold epithelial cells, resulted in severe morphogenetic defects.

Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes.

Respiratory failure associated with COVID-19 has placed focus on the lungs. Here, we present single-nucleus accessible chromatin profiles of 90,980 nuclei and matched single-nucleus transcriptomes of 46,500 nuclei in non-diseased lungs from donors of ~30 weeks gestation,~3 years and ~30 years. We mapped candidate -regulatory elements (cCREs) and linked them to putative target genes.

Smooth Muscle Differentiation Is Essential for Airway Size, Tracheal Cartilage Segmentation, but Dispensable for Epithelial Branching.

Airway smooth muscle is best known for its role as an airway constrictor in diseases such as asthma. However, its function in lung development is debated. A prevalent model, supported by in vitro data, posits that airway smooth muscle promotes lung branching through peristalsis and pushing intraluminal fluid to branching tips.

E3 ubiquitin ligase MDM2 acts through p53 to control respiratory progenitor cell number and lung size.

The respiratory lineage initiates from the specification of NKX2-1 progenitor cells that ultimately give rise to a vast gas-exchange surface area. How the size of the progenitor pool is determined and whether this directly impacts final lung size remains poorly understood. Here, we show that epithelium-specific inactivation of , which encodes an E3 ubiquitin ligase, led to lethality at birth with a striking reduction of lung size to a single vestigial lobe.

Crouzon syndrome mouse model exhibits cartilage hyperproliferation and defective segmentation in the developing trachea.

Crouzon syndrome is the result of a gain-of-function point mutation in FGFR2. Mimicking the human mutation, a mouse model of Crouzon syndrome (Fgfr) recapitulates patient deformities, including failed tracheal cartilage segmentation, resulting in a cartilaginous sleeve in the homozygous mutants. We found that the Fgfr2 mutants exhibited an increase in chondrocytes prior to segmentation.

Consider the lung as a sensory organ: A tip from pulmonary neuroendocrine cells.

While the lung is commonly known for its gas exchange function, it is exposed to signals in the inhaled air and responds to them by collaborating with other systems including immune cells and the neural circuit. This important aspect of lung physiology led us to consider the lung as a sensory organ. Among different cell types within the lung that mediate this role, several recent studies have renewed attention on pulmonary neuroendocrine cells (PNECs).

inactivation reveals Hippo function in alveolar type I cell differentiation during lung transition to air breathing.

Lung growth to its optimal size at birth is driven by reiterative airway branching followed by differentiation and expansion of alveolar cell types. How this elaborate growth is coordinated with the constraint of the chest is poorly understood. Here, we investigate the role of Hippo signaling, a cardinal pathway in organ size control, in mouse lung development.

β-Catenin signaling is essential for mammalian larynx recanalization and the establishment of vocal fold progenitor cells.

Congenital laryngeal webs result from failure of vocal fold separation during development Infants present with life-threatening respiratory problems at birth, and extensive lifelong difficulties in breathing and voicing. The molecular mechanisms that instruct vocal fold formation are rarely studied. Here, we show, for the first time, that conditional inactivation of the gene encoding β-catenin in the primitive laryngopharyngeal epithelium leads to failure in separation of the vocal folds, which approximates the gross phenotype of laryngeal webbing.

Embryology meets molecular biology: Deciphering the apical ectodermal ridge.

More than sixty years ago, while studying feather tracks on the shoulder of the chick embryo, Dr. John Saunders used Nile Blue dye to stain the tissue. There, he noticed a darkly stained line of cells that neatly rims the tip of the growing limb bud.

E3 ubiquitin ligase RFWD2 controls lung branching through protein-level regulation of ETV transcription factors.

The mammalian lung is an elaborate branching organ, and it forms following a highly stereotypical morphogenesis program. It is well established that precise control at the transcript level is a key genetic underpinning of lung branching. In comparison, little is known about how regulation at the protein level may play a role.

Syndactyly in a novel Fras1(rdf) mutant results from interruption of signals for interdigital apoptosis.

Background: Fras1 encodes an extracellular matrix protein that is critical for the establishment of the epidermal basement membrane during gestation. In humans, mutations in FRAS1 cause Fraser Syndrome (FS), a pleiotropic condition with many clinical presentations such as limb, eye, kidney, and craniofacial deformations. Many of these defects are mimicked by loss of Fras1 in mice, and are preceded by the formation of epidermal blisters in utero.

Pulmonary neuroendocrine cells function as airway sensors to control lung immune response.

The lung is constantly exposed to environmental atmospheric cues. How it senses and responds to these cues is poorly defined. Here, we show that Roundabout receptor (Robo) genes are expressed in pulmonary neuroendocrine cells (PNECs), a rare, innervated epithelial population.

A three-dimensional study of alveologenesis in mouse lung.

Alveologenesis is the final step of lung maturation, which subdivides the alveolar region of the lung into smaller units called alveoli. Each of the nascent dividers serves as a new gas-exchange surface, and collectively they drastically increase the surface area for breathing. Disruption of alveologenesis results in simplification of alveoli, as is seen in premature infants diagnosed with bronchopulmonary dysplasia (BPD), a prevalent lung disease that is often associated with lifelong breathing deficiencies.

Genomic Analyses of Sperm Fate Regulator Targets Reveal a Common Set of Oogenic mRNAs in Caenorhabditis elegans.

Germ cell specification as sperm or oocyte is an ancient cell fate decision, but its molecular regulation is poorly understood. In Caenorhabditis elegans, the FOG-1 and FOG-3 proteins behave genetically as terminal regulators of sperm fate specification. Both are homologous to well-established RNA regulators, suggesting that FOG-1 and FOG-3 specify the sperm fate post-transcriptionally.

FGF-Regulated ETV Transcription Factors Control FGF-SHH Feedback Loop in Lung Branching.

The mammalian lung forms its elaborate tree-like structure following a largely stereotypical branching sequence. While a number of genes have been identified to play essential roles in lung branching, what coordinates the choice between branch growth and new branch formation has not been elucidated. Here we show that loss of FGF-activated transcription factor genes, Etv4 and Etv5 (collectively Etv), led to prolonged branch tip growth and delayed new branch formation.

Ontogeny of the mouse vocal fold epithelium.

This investigation provides the first systematic determination of the cellular and molecular progression of vocal fold (VF) epithelium development in a murine model. We define five principal developmental events that constitute the progression from VF initiation in the embryonic anterior foregut tube to fully differentiated and functional adult tissue. These developmental events include (1) the initiation of the larynx and vocal folds with apposition of the lateral walls of the primitive laryngopharynx (embryonic (E) day 10.

Comparison of temporal transcriptomic profiles from immature lungs of two rat strains reveals a viral response signature associated with chronic lung dysfunction.

Early life respiratory viral infections and atopic characteristics are significant risk factors for the development of childhood asthma. It is hypothesized that repeated respiratory viral infections might induce structural remodeling by interfering with the normal process of lung maturation; however, the specific molecular processes that underlie these pathological changes are not understood. To investigate the molecular basis for these changes, we used an established Sendai virus infection model in weanling rats to compare the post-infection transcriptomes of an atopic asthma susceptible strain, Brown Norway, and a non-atopic asthma resistant strain, Fischer 344.

Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia.

Neurodegenerative diseases, such as frontotemporal dementia (FTD), are often associated with behavioral deficits, but the underlying anatomical and molecular causes remain poorly understood. Here we show that forebrain-specific expression of FTD-associated mutant CHMP2B in mice causes several age-dependent neurodegenerative phenotypes, including social behavioral impairments. The social deficits were accompanied by a change in AMPA receptor (AMPAR) composition, leading to an imbalance between Ca(2+)-permeable and Ca(2+)-impermeable AMPARs.

Establishment of smooth muscle and cartilage juxtaposition in the developing mouse upper airways.

In the trachea and bronchi of the mouse, airway smooth muscle (SM) and cartilage are localized to complementary domains surrounding the airway epithelium. Proper juxtaposition of these tissues ensures a balance of elasticity and rigidity that is critical for effective air passage. It is unknown how this tissue complementation is established during development.