Retinoic acid signalling is a candidate regulator of the expression of pituitary-specific transcription factor Prop1 in the developing rodent pituitary

Retinoic acid signalling is a candidate regulator of the expression of pituitary-specific transcription factor Prop1 in the developing rodent pituitary
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DOI:
10.1111/jne.12570
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发表时间:
2018-03-01
影响因子:
3.2
通讯作者:
Kato, Y.
Kato, Y.
中科院分区:
医学3区
文献类型:
--
作者:
Yoshida, S.;Fujiwara, K.;Kato, Y.

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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)作为脊椎动物许多组织器官发生的重要信号分子。然而,人们对发育中垂体的靶基因知之甚少。本研究旨在阐明 Rathke 囊垂体原基中内源性 RA 信号传导与垂体特异性转录因子 Prop1 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 囊中的转录水平上表达。使用 Rathke 袋进行的离体器官培养和体外报告基因测定表明,RA 信号通过 RAR 增加 Prop1 的表达水平。此外,使用小鼠 Prop1 5-上游区域的连续截短构建体进行的报告分析揭示了预测的 RAR 顺式调控元件。这是关于早期垂体发育过程中 RA 信号传导与 Prop1 表达之间关系的第一份报告。
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 RAR. Moreover, a reporter assay using serial truncated constructs of the 5-upstream region of mouse Prop1 revealed a predicted cis-regulatory element of RAR. This is the first report of a relationship between RA signalling and Prop1-expression during early pituitary development.