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: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:The existence and function of Lgr5+ cells within the developing esophagus remains unknown. Here, we document multiple discrete Lgr5+ populations in the developing mouse esophagus, predominantly within nascent epithelial and external muscle layers. Lgr5 expression initially emerges in the developing proximal embryonic epithelium, but progressively extends distally and persists within the distal epithelium of neonates. Fate mapping and ablation analyses reveal a long-term contribution of epithelial Lgr5+ cells to esophageal organogenesis. Additionally, Lgr5-expressing cells are present in the developing external muscle layer, particularly during the development of the striated component. Fate mapping reveals a significant contribution of these embryonic Lgr5+ cells to the adult muscle layer. Embryonic Lgr5+ epithelial cells are also found to be important for regulating epithelial development, serving as a key source of Wnt6, among other ligands, to promote epithelial cell proliferation and formation of epithelial layers. These findings significantly enhance our understanding of esophageal development and shed light on the involvement of Lgr5+ stem/progenitor cells during organogenesis. Importantly, this study lays the foundation for investigating esophageal diseases related to the Lgr5+ stem/progenitor cell pool.
Project description:The existence and function of Lgr5+ cells within the developing esophagus remains unknown. Here, we document multiple discrete Lgr5+ populations in the developing mouse esophagus, predominantly within nascent epithelial and external muscle layers. Lgr5 expression initially emerges in the developing proximal embryonic epithelium, but progressively extends distally and persists within the distal epithelium of neonates. Fate mapping and ablation analyses reveal a long-term contribution of epithelial Lgr5+ cells to esophageal organogenesis. Additionally, Lgr5-expressing cells are present in the developing external muscle layer, particularly during the development of the striated component. Fate mapping reveals a significant contribution of these embryonic Lgr5+ cells to the adult muscle layer. Embryonic Lgr5+ epithelial cells are also found to be important for regulating epithelial development, serving as a key source of Wnt6, among other ligands, to promote epithelial cell proliferation and formation of epithelial layers. These findings significantly enhance our understanding of esophageal development and shed light on the involvement of Lgr5+ stem/progenitor cells during organogenesis. Importantly, this study lays the foundation for investigating esophageal diseases related to the Lgr5+ stem/progenitor cell pool.
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: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: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:We show that striated muscle-expressed genes affected by reduction in UNC-120/SRF activity are not similarly affected by absence of the FHOD-1 formin. This suggests FHOD-1 does not affect striated muscle development via promotion of UNC-120/SRF-dependent transcription.