Imprinted Dlk1 dosage as a size determinant of the mammalian pituitary gland.
Imprinted Dlk1 dosage as a size determinant of the mammalian pituitary gland.
复制标题
DOI：
10.7554/elife.84092
复制
发表时间：
2023-08-17
期刊：
影响因子：
7.7
通讯作者：
Charalambous M
中科院分区：
文献类型：
--
作者：
Scagliotti V;Vignola ML;Willis T;Howard M;Marinelli E;Gaston-Massuet C;Andoniadou C;Charalambous M
印记基因网络的共调节基因参与控制生长和身体大小，印记基因功能障碍是涉及内分泌系统的人类儿科疾病的基础。印记基因在脑垂体中高度表达，其中，Dlk 1是一种父系表达基因，其膜结合和分泌的蛋白产物可以调节多种干细胞群体的增殖和分化。循环DLK1的剂量先前已经通过未知的分子机制参与生长的控制。在这里，我们生成了一系列小鼠遗传模型，以修改垂体中Dlk 1表达水平，并证明DLK 1的剂量调节干细胞定型过程，对垂体大小产生终身影响。我们确定干细胞是DLK1的关键来源，胚胎破坏改变了垂体前叶的增殖，导致对以后生活中生长激素分泌的长期影响。
Co-regulated genes of the Imprinted Gene Network are involved in the control of growth and body size, and imprinted gene dysfunction underlies human paediatric disorders involving the endocrine system. Imprinted genes are highly expressed in the pituitary gland, among them, Dlk1, a paternally expressed gene whose membrane-bound and secreted protein products can regulate proliferation and differentiation of multiple stem cell populations. Dosage of circulating DLK1 has been previously implicated in the control of growth through unknown molecular mechanisms. Here we generate a series of mouse genetic models to modify levels of Dlk1 expression in the pituitary gland and demonstrate that the dosage of DLK1 modulates the process of stem cell commitment with lifelong impact on pituitary gland size. We establish that stem cells are a critical source of DLK1, where embryonic disruption alters proliferation in the anterior pituitary, leading to long-lasting consequences on growth hormone secretion later in life.
影响因子：
2.6
作者：
Appelbe, Oliver K.;Yevtodiyenko, Aleksey;Muniz-Talavera, Hilmarie;Schmidt, Jennifer V.
通讯作者：
Schmidt, Jennifer V.
影响因子：
3.2
作者：
Cheung LY;Rizzoti K;Lovell-Badge R;Le Tissier PR
通讯作者：
Le Tissier PR