A novel role for cilia-dependent sonic hedgehog signaling during submandibular gland development.
A novel role for cilia-dependent sonic hedgehog signaling during submandibular gland development.
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DOI：
10.1002/dvdy.24627
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Brugmann SA
中科院分区：
文献类型：
--
作者：
Elliott KH;Millington G;Brugmann SA
下颌下腺（SMG）是专门的上皮结构，其产生咀嚼和消化所必需的唾液。SMG的丧失可导致炎症、口腔病变、真菌感染、咀嚼/吞咽问题和蛀牙。了解SMG的发展对于为SMG功能受损的患者制定治疗方案非常重要。最近的研究表明，上皮中的Sonic hedgehog（Shh）信号在SMG发育中起着不可或缺的作用;然而，Shh影响腺体发育的机制仍然模糊不清。使用Kif 3af/f; Wnt 1-Cre ciliopathic小鼠模型，以防止Shh信号转导通过初级纤毛在神经嵴细胞的损失，我们报告说，间充质Shh活动是必要的腺体发育。此外，使用各种小鼠转基因株系异常间充质Shh信号转导，我们确定，Shh活性的损失，通过Gli激活剂的损失，而不是Gli阻遏物的增益，足以导致SMG发育不全。最后，我们确定SMG的丢失与神经调节蛋白1（Nrg 1）表达减少和SMG上皮神经支配的缺乏相关。总之，这些数据表明了SMG发育过程中间充质Shh信号传导的新机制作用。
Submandibular glands (SMGs) are specialized epithelial structures which generate saliva necessary for mastication and digestion. Loss of SMGs can lead to inflammation, oral lesions, fungal infections, problems with chewing/swallowing, and tooth decay. Understanding the development of the SMG is important for developing therapeutic options for patients with impaired SMG function. Recent studies have suggested Sonic hedgehog (Shh) signaling in the epithelium plays an integral role in SMG development; however, the mechanism by which Shh influences gland development remains nebulous. Using the Kif3af/f;Wnt1-Cre ciliopathic mouse model to prevent Shh signal transduction via the loss of primary cilia in neural crest cells, we report that mesenchymal Shh activity is necessary for gland development. Furthermore, using a variety of murine transgenic lines with aberrant mesenchymal Shh signal transduction, we determine that loss of Shh activity, via loss of the Gli activator, rather than gain of Gli repressor, is sufficient to cause the SMG aplasia. Finally, we determine that loss of the SMG correlates with reduced Neuregulin1 (Nrg1) expression and lack of innervation of the SMG epithelium. Together, these data suggest a novel mechanistic role for mesenchymal Shh signaling during SMG development.
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DOI：
10.1038/nrm3528
发表时间：
2013-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.3
作者：
Falkenstein, Kristin N.;Vokes, Steven A.
通讯作者：
Vokes, Steven A.
影响因子：
2.7
作者：
Chiang, C;Swan, RZ;Dlugosz, AA
通讯作者：
Dlugosz, AA
影响因子：
3.5
作者：
Böse, J;Grotewold, L;Rüther, U
通讯作者：
Rüther, U
影响因子：
4.5
作者：
Chang CF;Chang YT;Millington G;Brugmann SA
通讯作者：
Brugmann SA