Early embryogenesis in CHDFIDD mouse model reveals facial clefts and altered craniofacial neurogenesis

Author:

Hampl M,Jandova N,Luskova D,Novakova M,Prochazka J,Kohoutek J,Buchtova MORCID

Abstract

ABSTRACTCongenital heart defects, facial dysmorphism and intellectual development disorder (CHDFIDD) is associated with mutations inCDK13gene which encodes a transcription regulating Cyclin-dependent kinase 13 (CDK13). Here we analyzed early embryonic stages of CHDFIDD mouse models with hypomorphic mutation inCdk13gene with very similar phenotypic manifestations plus cleft lip/palate and knockout ofCdk13which exhibits robust phenotype with midfacial cleft.Cdk13is strongly expressed in the mouse embryonic craniofacial structures, namely in the forebrain, nasal epithelium and maxillary mesenchyme.In vitro,CDK13 protein is located not only in nuclear region but also in the cellular protrusions in cultured mesenchymal cells and cells isolated from dorsal root ganglia. InCdk13-deficient embryos, we found hypoplastic branches of the trigeminal nerve including maxillary branch and additionally we detected significant gene expression changes of molecules involved in neurogenesis (Mef2c,Pou4f1,Sod1,Cdk5rap2,Nrcam) within the developing palatal shelves. Key palate-associated molecules (Msx1andMeis2) were downregulated during early craniofacial development in mutant embryos. These results demonstrate the role of CDK13 in regulation of facial morphogenesis and also growth of craniofacial peripheral nerves.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3