Division of Pathology, Department of Oral Diagnostic Sciences, Showa University School of Dentistry, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
Division of Pathology, Department of Oral Diagnostic Sciences, Showa University School of Dentistry, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
J Oral Biosci. 2021 Mar;63(1):8-13. doi: 10.1016/j.job.2021.01.005. Epub 2021 Jan 23.
Organogenesis is regulated by morphogen signaling and transcription networks. These networks differ between organs, and identifying the organ-specific network is important to clarify the molecular mechanisms of development and regeneration of organs. Several studies have been conducted to identify salivary gland-specific networks using a mouse submandibular gland model. The submandibular glands (SMGs) of mice manifest as a thickening of the oral epithelium at embryonic day 11.5 and invaginate into the underlying mesenchyme. The network between Fgf10 and Sox9 is involved in SMG development in mice.
Sox9, a member of the Sox family, is expressed in the SMG in mice from the embryonic stage to the adult stage, although the distribution changes during development. A null mutation of mouse Sox9 is lethal during the neonatal period due to respiratory failure, whereas deletion of Sox9 in the oral epithelium using the Cre/lox P system, can lead to smaller initial buds of SMGs in conditional knockout (cKO) mice than in normal mice. In addition, we showed that adenoviral transduction of Sox9 and Foxc1 genes into mouse embryonic stem cell-derived oral ectoderm could induce salivary gland rudiment in an organoid culture system. ChIP-sequencing revealed that Sox9 possibly regulates several tube- and branching-formation-related genes.
Sox9 may serve as an essential transcription factor for salivary gland development. The Sox9-mediated pathway can be a promising candidate for regenerating damaged salivary glands.
器官发生受形态发生素信号和转录网络的调节。这些网络在器官之间存在差异，确定器官特异性网络对于阐明器官发育和再生的分子机制非常重要。已经有几项研究使用小鼠下颌下腺模型来鉴定唾液腺特异性网络。小鼠的下颌下腺（SMG）在胚胎第 11.5 天表现为口腔上皮的增厚，并向下方的间充质内陷。Fgf10 和 Sox9 之间的网络参与了小鼠 SMG 的发育。
Sox9 是 Sox 家族的成员，在小鼠的 SMG 中从胚胎期到成年期表达，尽管在发育过程中分布发生变化。由于呼吸衰竭，Sox9 基因在小鼠中发生缺失突变会导致新生期致死，而使用 Cre/lox P 系统在口腔上皮中缺失 Sox9 会导致条件性敲除（cKO）小鼠的 SMG 初始芽比正常小鼠小。此外，我们表明，将 Sox9 和 Foxc1 基因的腺病毒转导到小鼠胚胎干细胞衍生的口腔外胚层中，可以在类器官培养系统中诱导唾液腺原基的形成。ChIP-seq 表明 Sox9 可能调节几个管和分支形成相关基因。
Sox9 可能作为唾液腺发育的必需转录因子。Sox9 介导的途径可能是再生受损唾液腺的有前途的候选途径。
