Wendt Kristy D, Brown Jared, Lungova Vlasta, Mohad Vidisha, Kendziorski Christina, Thibeault Susan L
Department of Surgery, Division of Otolaryngology, Head, and Neck Surgery, University of Wisconsin, Madison, WI, United States.
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States.
Front Cell Dev Biol. 2022 Jul 22;10:942622. doi: 10.3389/fcell.2022.942622. eCollection 2022.
The larynx, trachea, and esophagus share origin and proximity during embryonic development. Clinical and experimental evidence support the existence of neurophysiological, structural, and functional interdependencies before birth. This investigation provides the first comprehensive transcriptional profile 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. By applying bulk RNA sequencing and gene network analysis of differentially expressed genes (DEGs) 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 adulthood is characterized in the context of laryngeal organogenesis. The findings of this study provide new insights into interrelated gene sets governing the organogenesis of this tripartite organ system within the aerodigestive tract. They are relevant to multiple families of disorders defined by cardiocraniofacial syndromes.
在胚胎发育过程中，喉、气管和食管起源相同且位置相近。临床和实验证据支持在出生前它们存在神经生理、结构和功能上的相互依存关系。本研究提供了胚胎器官发生过程中这三个器官的首个全面转录图谱，在此过程中，差异基因表达从前肠前部的共同起源逐渐塑造了这些相邻器官的特性和复杂性。通过对发育中的胚胎小鼠喉、食管和气管内部及之间的差异表达基因（DEG）进行批量RNA测序和基因网络分析，我们确定了富含关键生物学过程的共表达基因模块。描述了胚胎发育期间（E10.5 - E18.5）共享组织内部及之间与基因模块相对应的器官特异性基因活动时间模式，并在喉器官发生的背景下对从出生到成年的声带发育和成熟过程中的喉转录组进行了表征。本研究结果为调控这一位于气消化道内的三联器官系统器官发生的相关基因集提供了新见解。它们与由心脏颅面综合征定义的多个疾病家族相关。
