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Abstract：
CDK13-related disorder, also known as congenital heart defects, dysmorphic facial features and intellectual developmental disorder (CHDFIDD) is associated with mutations in the CDK13 gene encoding transcription-regulating cyclin-dependent kinase 13 (CDK13). Here, we focused on the development of craniofacial structures and analyzed early embryonic stages in CHDFIDD mouse models, with one model comprising a hypomorphic mutation in Cdk13 and exhibiting cleft lip/palate, and another model comprising knockout of Cdk13, featuring a stronger phenotype including midfacial cleft. Cdk13 was found to be physiologically expressed at high levels in the mouse embryonic craniofacial structures, namely in the forebrain, nasal epithelium and maxillary mesenchyme. We also uncovered that Cdk13 deficiency leads to development of hypoplastic branches of the trigeminal nerve including the maxillary branch. Additionally, we detected significant changes in the expression levels of genes involved in neurogenesis (Ache, Dcx, Mef2c, Neurog1, Ntn1, Pou4f1) within the developing palatal shelves. These results, together with changes in the expression pattern of other key face-specific genes (Fgf8, Foxd1, Msx1, Meis2 and Shh) at early stages in Cdk13 mutant embryos, demonstrate a key role of CDK13 in the regulation of craniofacial morphogenesis.
摘要：
CDK13相关疾病,也被称为先天性心脏缺陷，畸形面部特征和智力发育障碍（CHDFIDD）与编码转录调节细胞周期蛋白依赖性激酶13（CDK13）的CDK13基因突变有关。这里,我们专注于颅面结构的发育，并分析了CHDFIDD小鼠模型的早期胚胎阶段，其中一个模型包含Cdk13的低态突变，并表现出唇裂/腭裂，和另一个包含敲除Cdk13的模型，具有更强的表型，包括中面裂。发现Cdk13在小鼠胚胎颅面结构中在生理上高水平表达，即在前脑，鼻上皮和上颌间质。我们还发现Cdk13缺乏导致三叉神经的发育不良分支，包括上颌分支。此外,我们检测到参与神经发生的基因表达水平的显著变化（Ache，Dcx,Mef2c,Neurog1，Ntn1，Pou4f1）在发育中的腭架内。这些结果,以及Cdk13突变胚胎早期阶段其他关键面部特异性基因（Fgf8，Foxd1，Msx1，Meis2和Shh）的表达模式的变化，显示CDK13在颅面形态发生的调节中的关键作用。
