Project description:The larynx, trachea, and esophagus share origin and proximity during embryonic development, with clinical and experimental evidence supporting the existence of neurophysiological, structural, and functional interdependencies before birth. This investigation provides the first comprehensive transcriptional profiling of all three organs during embryonic organogenesis, where differential gene expression gradually assembles the identity and complexity of these proximal organs from a shared origin in the anterior foregut. Through the application of bulk RNA sequencing and gene network analysis of differentially expressed genes (DEGs), both within and across developing embryonic mouse larynx, esophagus, and trachea, we identified co-expressed modules of genes enriched for key biological processes. Organ-specific temporal patterns of gene activity corresponding to gene modules within and across shared tissues during embryonic development (E10.5-E18.5) are described, and the laryngeal transcriptome during vocal fold development and maturation from birth to adult is characterized in the context of laryngeal organogenesis. The findings of this study provide new insights into interrelated gene sets governing organogenesis of this tripartite organ system within the aerodigestive tract, with relevance to multiple families of disorders defined by cardiocraniofacial syndromes.
Project description:Ion channels play critical roles in the physiology and function of the nervous system and contractile tissue; however, their role in non-contractile tissue and embryonic development has yet to be understood. Tracheobronchomalacia (TBM) and complete tracheal rings (CTR) are disorders affecting the muscle and cartilage of the trachea and bronchi, whose etiology remains poorly understood. We demonstrated that trachealis muscle organization and polarity are disrupted after epithelial ablation of Wls, a cargo receptor critical for the Wnt signaling pathway, in developing trachea. The phenotype resembles the anomalous trachealis muscle observed after deletion of ion channel encoding genes in developing mouse trachea. We sought to investigate whether and how the deletion ofWlsaffects ion channels during tracheal development. We hypothesize that Wnt signaling influences the expression of ion channels to promote trachealis muscle cell assembly and patterning. Deleting Wls in developing trachea causes differential regulation of genes mediating actin binding, cytoskeleton organization, and potassium ion channel activity. Wnt signaling regulated expression of Kcnj13, Kcnd3, Kcnj8, and Abcc9 as demonstrated by in vitro studies and in vivo analysis in Wnt5a and b-catenin deficient tracheas. Pharmacological inhibition of potassium ion channels and Wnt signaling impaired contractility of developing trachealis smooth muscle and formation of cartilaginous mesenchymal condensation. Thus, in mice, epithelial-induced Wnt/b-catenin signaling mediates trachealis muscle and cartilage development via modulation of ion channel expression, promoting trachealis muscle architecture, contractility, and cartilaginous extracellular matrix. In turn, ion channel activity may influence tracheal morphogenesis underlying TBM and CTR.
Project description:Barrett's esophagus transcriptome was analysed and compared with Barrett's esophagus primary cell culture and esophageal adenocarcinoma. Keywords: SAGE analysis to compare tissues Barrett's esophagus biopsy was taken from 1 male metaplastic Barrett's esophagus patient. Barrett's esophagus primary cell culture was cultures from a biopsy taken from a Barrett's esophagus patient and cultured for about 4 to 5 weeks. Esophageal adenocarcinoma was taken from a patient known to have cancer and previously Barrett's esophagus
Project description:Barrett's esophagus is a metaplastic condition of the distal esophagus, characterized by the replacement of normal squamous epithelium by columnar epithelium. Patients with BE have an increased risk of developing esophageal adenocarcinoma. MicroRNAs have been implicated to be disease and tissue specific, however limited data of microRNA expression in the esophagus is available. Therefore we evaluated microRNA expression profiles of esophageal adenocarcinoma and compared these with Barrett's esophagus and normal squamous esophagus.
Project description:SAGE libraries made of squamous esophagus tissue, primary cell culture or esophageal squamous cell carcinoma Keywords: SAGE analysis of different tissues squamous esophagus biopsy was taken from 1 male metaplastic Barrett's esophagus patient. primary cell culture was from 1 male Barrett's esophagus patient. Esophageal squamous cell carcinoma was from a patient known to have ESCC
Project description:SAGE performed on biopsies of Barrett's esophagus, squamous esophagus and gastric cardia taken from a metaplastic Barrett's esophagus patient. Keywords: SAGE comparative analysis of gene expression profiles of Barrett's esophagus, normal squamous esophagus and gastric cardia tissue
Project description:The esophagus is a muscular tube which transports swallowed content from the oral cavity and the pharynx to the stomach. Early in mouse development, an entire layer of the esophagus, the muscularis externa, consists of differentiated smooth muscle cells. Starting shortly after mid-gestation till about two weeks after birth, the muscularis externa almost entirely consists of striated muscle. This proximal-to-distal replacement of smooth muscle by the striated muscle depends on a number of factors. To identify the nature of the hypothetical “proximal” (mainly striated muscle originating) and “distal” (mainly smooth muscle originating) signals that govern the striated-for-smooth muscle replacement, we compared the esophagus of Myf5:MyoD null fetuses completely lacking striated muscle to the normal control using cDNA microarray analysis, followed by a comprehensive databases search. Here we provide an insight into the nature of “proximal” and “distal” signals that govern the striated-for-smooth muscle replacement in the esophagus.
Project description:Scnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells. The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93; Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84; and Livraghi-Butrico et al. 2012, Mucosal Immunology 5(4):397-408). Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, which causes airway surface liquid and mucus dehydration, resulting in reduced mucus clearance and airway mucus obstruction. The data provided here represents mRNA expression data from dissected whole trachea (distal and proximal ends were cut 3-4 cartilage rings below the larynx and just above the bifurcation, respectively) from male WT and Scnn1b-Tg littermates (C57Bl/6N Tac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42]. Histologically, PND 0 trachea are normal, a tracheal mucus plug/obstruction develops around PND 3 and typically recedes to the intrapulmonary airways after PND 10, and the trachea is again histologically normal by PND 42. The data from the WT mice provides a global look at mRNA post-natal developmental changes, while the data from the Scnn1b-Tg line provides mRNA data that allows differential gene expression due to airway mucus obstruction to be queried. The data presented for the trachea is part of a larger body of work evaluating gene expression in whole lung, trachea, and purified macrophages.
Project description:The peptide-level analysis of proteome and secretome changes of mouse trachea cells upon denatonium treatment (in comparison to Ringer lactate solution control).