Liu J, Lin C, Gleiberman A, Ohgi K A, Herman T, Huang H P, Tsai M J, Rosenfeld M G
Howard Hughes Medical Institute, School and Department of Medicine, University of California at San Diego, 9500 Gilman Drive, Cellular and Molecular Medicine West, Room 345, La Jolla, CA 92093-0648, USA.
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8674-9. doi: 10.1073/pnas.141234898. Epub 2001 Jul 10.
Pituitary cell types arise in a temporally and spatially specific fashion, in response to combinatorial actions of transcription factors induced by transient signaling gradients. The critical transcriptional determinants of the two pituitary cell types that express the pro-opiomelanocortin (POMC) gene, the anterior lobe corticotropes, producing adrenocorticotropin, and the intermediate lobe melanotropes, producing melanocyte-stimulating hormone (MSH alpha), have remained unknown. Here, we report that a member of the T-box gene family, Tbx19, which is expressed only in the rostral ventral diencephalon and pituitary gland, commencing on e11.5, marks pituitary cells that will subsequently express the POMC gene and is capable of altering progression of ventral cell types and inducing adrenocorticotropin in rostral tip cells. It is suggested that Tbx19, depending on the presence of synergizing transcription factors, can activate POMC gene expression and repress the alpha glycoprotein subunit and thyroid-stimulating hormone beta promoters.
垂体细胞类型以时间和空间特异性的方式产生,以响应由短暂信号梯度诱导的转录因子的组合作用。表达促肾上腺皮质激素原(POMC)基因的两种垂体细胞类型,即产生促肾上腺皮质激素的前叶促肾上腺皮质激素细胞和产生促黑素细胞激素(α-MSH)的中间叶促黑素细胞,其关键转录决定因素仍然未知。在这里,我们报告T-box基因家族的一个成员Tbx19,它仅在胚胎第11.5天开始在吻侧腹侧间脑和垂体中表达,标记随后将表达POMC基因的垂体细胞,并且能够改变腹侧细胞类型的进程并在吻端细胞中诱导促肾上腺皮质激素。有人认为,取决于协同转录因子的存在,Tbx19可以激活POMC基因表达并抑制α糖蛋白亚基和促甲状腺激素β启动子。