Keil Kimberly P, Altmann Helene M, Mehta Vatsal, Abler Lisa L, Elton Erik A, Vezina Chad M
Department of Comparative Biosciences, University of Wisconsin-Madison, 1656 Linden Dr., Madison, WI 53706, USA.
Gene Expr Patterns. 2013 Dec;13(8):413-24. doi: 10.1016/j.gep.2013.07.008. Epub 2013 Aug 3.
The mouse prostate develops from a component of the lower urinary tract (LUT) known as the urogenital sinus (UGS). This process requires androgens and signaling between mesenchyme and epithelium. Little is known about DNA methylation during prostate development, including which factors are expressed, whether their expression changes over time, and if DNA methylation contributes to androgen signaling or influences signaling between mesenchyme and epithelium. We used in situ hybridization to evaluate the spatial and temporal expression pattern of mRNAs which encode proteins responsible for establishing, maintaining or remodeling DNA methylation. These include DNA methyltransferases, DNA deaminases, DNA glycosylases, base excision repair and mismatch repair pathway members. The mRNA expression patterns were compared between male and female LUT prior to prostatic bud formation (14.5 days post coitus (dpc)), during prostatic bud formation (17.5 dpc) and during prostatic branching morphogenesis (postnatal day (P) 5). We found dramatic changes in the patterns of these mRNAs over the course of prostate development and identified examples of sexually dimorphic mRNA expression. Future investigation into how DNA methylation patterns are established, maintained and remodeled during the course of embryonic prostatic bud formation may provide insight into prostate morphogenesis and disease.
小鼠前列腺由下尿路(LUT)的一个组成部分即泌尿生殖窦(UGS)发育而来。这一过程需要雄激素以及间充质与上皮之间的信号传导。关于前列腺发育过程中的DNA甲基化知之甚少,包括哪些因子表达、它们的表达是否随时间变化,以及DNA甲基化是否有助于雄激素信号传导或影响间充质与上皮之间的信号传导。我们使用原位杂交来评估编码负责建立、维持或重塑DNA甲基化的蛋白质的mRNA的时空表达模式。这些包括DNA甲基转移酶、DNA脱氨酶、DNA糖基化酶、碱基切除修复和错配修复途径成员。在前列腺芽形成之前(交配后14.5天(dpc))、前列腺芽形成期间(17.5 dpc)和前列腺分支形态发生期间(出生后第(P)5天),比较了雄性和雌性LUT之间的mRNA表达模式。我们发现这些mRNA的模式在前列腺发育过程中发生了显著变化,并确定了性二态性mRNA表达的例子。未来对胚胎前列腺芽形成过程中DNA甲基化模式如何建立、维持和重塑的研究可能会为前列腺形态发生和疾病提供见解。