Centriolar Protein C2cd3 Is Required for Craniofacial Development.
Centriolar Protein C2cd3 Is Required for Craniofacial Development.
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DOI：
10.3389/fcell.2021.647391
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发表时间：
2021
影响因子：
5.5
通讯作者：
Brugmann SA
中科院分区：
文献类型：
--
作者：
Chang CF;Brown KM;Yang Y;Brugmann SA
初级纤毛是一种普遍存在的、基于微管的细胞器。原发性纤毛功能障碍导致一组疾病称为纤毛病。C2结构域包含3个中心粒伸长调节因子（C2cd3），编码一种纤毛发生所必需的中心粒蛋白。人类C2CD3基因突变与人类纤毛病口腔-面部-手指综合征14型（OFD14）有关。为了更好地了解包括OFD14在内的纤毛病的病因，我们建立了许多针对C2cd3的小鼠模型。最初的分析揭示了C2cd3的几种组织特异性亚型，虽然之前有报道称C2cd3的缺失会导致畸形、中脑紧张性弯曲、心包水肿、心环异常和体轴扭曲，但进一步的分析显示遗传背景也可能导致表型变异。针对C2cd3的c端PKC-C2结构域或n端C2CD3N-C2结构域的条件等位基因系列的进一步分析揭示了不同程度的表型严重程度，这表明尽管n端C2CD3N-C2结构域对整个早期胚胎发育至关重要，但C2CD3N-C2结构域也具有颅面特异性作用。总之，通过新模型的建立和C2cd3表达的评估，这些数据为颅面纤毛病的病理机制提供了有价值的见解，可以在未来进一步探索。
The primary cilium is a ubiquitous, microtubule-based cellular organelle. Primary cilia dysfunction results in a group of disorders termed ciliopathies. C2 domain containing 3 centriole elongation regulator (C2cd3), encodes a centriolar protein essential for ciliogenesis. Mutations in human C2CD3 are associated with the human ciliopathy Oral-Facial-Digital syndrome type 14 (OFD14). In order to better understand the etiology of ciliopathies including OFD14, we generated numerous murine models targeting C2cd3. Initial analysis revealed several tissue-specific isoforms of C2cd3, and while the loss of C2cd3 has previously been reported to result in exencephaly, tight mesencephalic flexure, pericardial edema, abnormal heart looping and a twisted body axis, further analysis revealed that genetic background may also contribute to phenotypic variation. Additional analyses of a conditional allelic series targeting C-terminal PKC-C2 domains or the N-terminal C2CD3N-C2 domain of C2cd3 revealed a variable degree of phenotypic severity, suggesting that while the N-terminal C2CD3N-C2 domain was critical for early embryonic development as a whole, there was also a craniofacial specific role for the C2CD3N-C2 domains. Together, through generation of novel models and evaluation of C2cd3 expression, these data provide valuable insight into mechanisms of pathology for craniofacial ciliopathies that can be further explored in the future.
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影响因子：
3.5
作者：
Kelemen O;Convertini P;Zhang Z;Wen Y;Shen M;Falaleeva M;Stamm S
通讯作者：
Stamm S
影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.1242/dev.029835
发表时间：
2008-12
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Hoover AN;Wynkoop A;Zeng H;Jia J;Niswander LA;Liu A
通讯作者：
Liu A
DOI：
10.1002/ajmg.c.30231
发表时间：
2009-11-15
影响因子：
3.1
作者：
Baker, Kate;Beales, Philip L.
通讯作者：
Beales, Philip L.
影响因子：
82.9
作者：
Jones, Natalie C.;Lynn, Megan L.;Trainor, Paul A.
通讯作者：
Trainor, Paul A.