Division of Life Science, Graduate School of Agriculture, Meiji University, Kawasaki, Kanagawa, Japan.
Organization for the Strategic Coordination of Research and Intellectual Property, Meiji University, Kawasaki, Kanagawa, Japan.
J Neuroendocrinol. 2018 Mar;30(3):e12570. doi: 10.1111/jne.12570.
Development of the anterior pituitary proceeds via spatiotemporal patterning of transcription factors and signalling molecules. Among them, retinoic acid (RA) functions as an important signalling molecule for vertebrate organogenesis in many tissues. However, little is known regarding the target genes in the developing pituitary. The present study aimed to clarify the relationship between endogenous RA signalling and mRNA expression of the pituitary-specific transcription factor Prop1 in the pituitary primordium of Rathke's pouch. Gene expression analysis and in situ hybridisation demonstrated that retinaldehyde dehydrogenases (Raldhs) and all types of RA receptors (Rars) are expressed at the level of transcription in the rat Rathke's pouch. Ex vivo organ culture using Rathke's pouch and an in vitro reporter assay demonstrated that RA signalling increases the expression level of Prop1 via RARα. Moreover, a reporter assay using serial truncated constructs of the 5'-upstream region of mouse Prop1 revealed a predicted cis-regulatory element of RARα. This is the first report of a relationship between RA signalling and Prop1-expression during early pituitary development.
垂体前叶的发育是通过转录因子和信号分子的时空模式进行的。其中,视黄酸(RA)作为许多组织中脊椎动物器官发生的重要信号分子。然而,对于发育中的垂体的靶基因知之甚少。本研究旨在阐明内源性 RA 信号与垂体特异性转录因子 Prop1 在 Rathke 囊垂体原基中的 mRNA 表达之间的关系。基因表达分析和原位杂交表明,视黄醛脱氢酶(Raldhs)和所有类型的 RA 受体(Rars)在大鼠 Rathke 囊转录水平表达。使用 Rathke 囊的离体器官培养和体外报告基因测定表明,RA 信号通过 RARα 增加 Prop1 的表达水平。此外,使用小鼠 Prop1 的 5'-上游区域的串联截断构建体进行的报告基因测定揭示了 RARα 的预测顺式调节元件。这是 RA 信号与早期垂体发育过程中 Prop1 表达之间关系的首次报道。