Fork head and Sage maintain a uniform and patent salivary gland lumen through regulation of two downstream target genes, PH4αSG1 and PH4αSG2
Fork head and Sage maintain a uniform and patent salivary gland lumen through regulation of two downstream target genes, PH4αSG1 and PH4αSG2
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DOI：
10.1242/dev.02525
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发表时间：
2006-09-15
期刊：
影响因子：
4.6
通讯作者：
Andrew, Deborah J.
中科院分区：
文献类型：
--
作者：
Abrams, Elliott W.;Mihoulides, Whitney K.;Andrew, Deborah J.
(Fkh) 是阻止唾液腺细胞凋亡、内化唾液腺前体、防止分泌细胞中导管基因表达以及维持 CrebA 表达（这是提高分泌功能所必需的）所必需的。在这里，我们描述了两个新的 Fkh 依赖性基因：PH4 α SG1 和 PH4 α SG2。我们通过体外 DNA 结合研究和体内表达测定表明，Fkh 与唾液腺特异性 bHLH 蛋白 Sage 合作，直接调节 PH4 α SG2 以及 Sage 本身的表达，并间接调节 PH4 α SG1 的表达。 PH4 α SG1 和 PH4 α SG2 编码驻留 ER 酶的 α 亚基，这些酶可羟化胶原蛋白和其他分泌蛋白中的脯氨酸。我们证明，在缺失 PH4 α SG1 和 PH4 α SG2 功能的胚胎中，唾液腺分泌发生了改变；分泌物含量减少，并且通过 TEM 显示电子密度增加。有趣的是，分泌内容的改变导致管扩张和收缩区域，并伴有间歇性管关闭。 PH4 α SG1 和 PH4 α SG2 的调控研究和表型特征将启动管形成的 Fkh 与维持开放且大小均匀的分泌管联系起来。
(Fkh) is required to block salivary gland apoptosis, internalize salivary gland precursors, prevent expression of duct genes in secretory cells and maintain expression of CrebA, which is required for elevated secretory function. Here, we characterize two new Fkh-dependent genes: PH4 alpha SG1 and PH4 alpha SG2. We show through in vitro DNA-binding studies and in vivo expression assays that Fkh cooperates with the salivary gland-specific bHLH protein Sage to directly regulate expression of PH4 alpha SG2, as well as sage itself, and to indirectly regulate expression of PH4 alpha SG1. PH4 alpha SG1 and PH4 alpha SG2 encode alpha-subunits of resident ER enzymes that hydroxylate prolines in collagen and other secreted proteins. We demonstrate that salivary gland secretions are altered in embryos missing function of PH4 alpha SG1 and PH4 alpha SG2; secretory content is reduced and shows increased electron density by TEM. Interestingly, the altered secretory content results in regions of tube dilation and constriction, with intermittent tube closure. The regulation studies and phenotypic characterization of PH4 alpha SG1 and PH4 alpha SG2 link Fkh, which initiates tube formation, to the maintenance of an open and uniformly sized secretory tube.