Supplementary Material for: From the Transcription of Genes Involved in Ectodermal Dysplasias to the Understanding of Associated Dental Anomalies

Orodental anomalies are one aspect of rare diseases and are increasingly identified as diagnostic and predictive traits. To understand the rationale behind gene expression during tooth or other ectodermal derivative development and the disruption of odontogenesis or hair and salivary gland formation in human syndromes we analyzed the expression patterns of a set of genes (Irf6, Nfkbia, Ercc3, Evc2, Map2k1) involved in human ectodermal dysplasias in mouse by in situ hybridization. The expression patterns of Nfkbia, Ercc3 and Evc2 during odontogenesis had never been reported previously. All genes were indeed transcribed in different tissues/organs of ectodermal origin. However, for Nfkbia, Ercc3, Evc2, and Map2k1, signals were also present in the ectomesenchymal components of the tooth germs. These expression patterns were consistent in timing and localization with the known dental anomalies (tooth agenesis, microdontia, conical shape, enamel hypoplasia) encountered in syndromes resulting from mutations in those genes. They could also explain the similar orodental anomalies encountered in some of the corresponding mutant mouse models. Translational approaches in development and medicine are relevant to gain understanding of the molecular events underlying clinical manifestations.

口腔颌面部异常（orodental anomalies）是罕见病的一类表现，且越来越多地被认定为具备诊断与预测价值的特征。为阐明牙齿或其他外胚层衍生物发育过程中基因表达的调控原理，以及人类综合征中牙发生、毛发与唾液腺形成的异常机制，我们通过原位杂交（in situ hybridization）技术，在小鼠模型中分析了一组与人类外胚层发育不良相关的基因（Irf6、Nfkbia、Ercc3、Evc2、Map2k1）的表达模式。此前尚未有关于Nfkbia、Ercc3及Evc2在牙发生过程中表达模式的相关报道。所有目标基因确实在不同外胚层来源的组织/器官中发生转录。然而，Nfkbia、Ercc3、Evc2及Map2k1的杂交信号同样出现在牙胚的外胚间充质成分中。这些表达模式在时间进程与空间定位上，与上述基因发生突变所引发的综合征中出现的已知牙颌面异常——牙缺失（tooth agenesis）、小牙症（microdontia）、锥形牙、釉质发育不全（enamel hypoplasia）——高度吻合。该结果同时可解释部分对应突变小鼠模型中出现的同类口腔颌面部异常表现。发育学与医学领域的转化研究方法，有助于阐明临床表型背后的分子调控事件。