Molecular Characterization of the Genital Organizer: Gene Expression Profile of the Mouse Urethral Plate Epithelium

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• 作者：Brooke A. Armfield^a ; Ashley W. Seifert^b ; ^&lowast ; ; Zhengui Zheng^a ; ^&dagger ; ; Emily M. Merton^a ; Jason R. Rock^a ; ^&Dagger ; ; Maria-Cecilia Lopez^a ; Henry V. Baker^a ; Martin J. Cohn^a ; ^b ; ^c ; ^{MJCohn@ufl.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：urethra ; genitalia ; gene expression ; microarray analysis ; congenital abnormalities
• 刊名：The Journal of Urology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：196
• 期：4
• 页码：1295-1302
• 全文大小：1430 K

文摘

Lower urinary tract malformations are among the most common congenital anomalies in humans. Molecular genetic studies of mouse external genital development have begun to identify mechanisms that pattern the genital tubercle and orchestrate urethral tubulogenesis. The urethral plate epithelium is an endodermal signaling region that has an essential role in external genital development. However, little is known about the molecular identity of this cell population or the genes that regulate its activity.

Materials and Methods

We used microarray analysis to characterize differences in gene expression between urethral plate epithelium and surrounding tissue in mouse genital tubercles. In situ hybridizations were performed to map gene expression patterns and ToppCluster (https://toppcluster.cchmc.org/) was used to analyze gene associations.

Results

A total of 84 genes were enriched at least 20-fold in urethral plate epithelium relative to surrounding tissue. The majority of these genes were expressed throughout the urethral plate in males and females at embryonic day 12.5 when the urethral plate is known to signal. Functional analysis using ToppCluster revealed genetic pathways with known functions in other organ systems but unknown roles in external genital development. Additionally, a 3-dimensional molecular atlas of genes enriched in urethral plate epithelium was generated and deposited at the GUDMAP (GenitoUrinary Development Molecular Anatomy Project) website (http://gudmap.org/).

Conclusions

We identified dozens of genes previously unknown to be expressed in urethral plate epithelium at a crucial developmental period. It provides a novel panel of genes for analysis in animal models and in humans with external genital anomalies.