A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development.
A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development.
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DOI：
10.3389/fphys.2018.01484
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发表时间：
2018
影响因子：
4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Kulkarni AK;Louie KW;Yatabe M;Ruellas ACO;Mochida Y;Cevidanes LHS;Mishina Y;Zhang H
Ellis-van Creveld（EvC）综合征是一种常染色体隐性遗传的软骨发育不良疾病。受影响的患者表现出广泛的症状，包括身材矮小，轴后多指（趾）畸形和牙齿异常。我们先前使用神经嵴特异性Cre介导的方法（即，P0-Cre，称为Evc 2 P0突变体）。尽管事实上，P0-Cre主要针对中面部区域，我们报告说，许多中面部缺陷中确定的Evc 2全球突变体不存在于出生后第8天（P8）的Evc 2 P0突变体。在目前的研究中，我们使用多个Cre线（分别为P0-Cre和Wnt 1-Cre），专门删除神经嵴衍生组织中的Evc 2，并比较多个时间点（分别为P8和P28）的面中部缺损。虽然两条Cre线都无可争议地瞄准了面中部区域，但它们不同地瞄准了颅底的前部。通过全面分析条件突变体头骨的形状，我们检测到差异影响面中部缺陷的Evc 2 P0突变体和Evc 2 Wnt 1突变体。对颅底的微型CT分析进一步揭示，Evc 2突变导致颅底受到差异性影响，这是由蝶骨间软骨结合（蝶骨前软骨结合）过早闭合引起的，这限制了出生后颅骨发育期间前颅底的伸长。头骨。鉴于颅底在面中部骨发育中的重要性，我们的研究结果表明，颅底内Evc 2功能的丧失继发性地导致EvC综合征引起的面中部缺损的许多方面。
Ellis-van Creveld (EvC) syndrome is an autosomal recessive chondrodysplastic disorder. Affected patients present a wide spectrum of symptoms including short stature, postaxial polydactyly, and dental abnormalities. We previously disrupted Evc2, one of the causative genes for EvC syndrome, in mice using a neural crest-specific, Cre-mediated approach (i.e., P0-Cre, referred to as Evc2 P0 mutants). Despite the fact that P0-Cre predominantly targets the mid-facial region, we reported that many mid-facial defects identified in Evc2 global mutants are not present in Evc2 P0 mutants at postnatal day 8 (P8). In the current study, we used multiple Cre lines (P0-Cre and Wnt1-Cre, respectively), to specifically delete Evc2 in neural crest-derived tissues and compared the resulting mid-facial defects at multiple time points (P8 and P28, respectively). While both Cre lines indistinguishably targeted the mid-facial region, they differentially targeted the anterior portion of the skull base. By comprehensively analyzing the shapes of conditional mutant skulls, we detected differentially affected mid-facial defects in Evc2 P0 mutants and Evc2 Wnt1 mutants. Micro-CT analysis of the skull base further revealed that the Evc2 mutation leads to a differentially affected skull base, caused by premature closure of the intersphenoid synchondrosis (presphenoidal synchondrosis), which limited the elongation of the anterior skull base during the postnatal development of the skull. Given the importance of the skull base in mid-facial bone development, our results suggest that loss of function of Evc2 within the skull base secondarily leads to many aspects of the mid-facial defects developed by the EvC syndrome.
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雌性 C57BL/6NCrl 小鼠产后颅面骨骼发育
影响因子：
4
作者：
Wei X;Thomas N;Hatch NE;Hu M;Liu F
通讯作者：
Liu F
影响因子：
3.7
作者：
Murgiano L;Jagannathan V;Benazzi C;Bolcato M;Brunetti B;Muscatello LV;Dittmer K;Piffer C;Gentile A;Drögemüller C
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Drögemüller C
DOI：
10.1002/ar.23353
发表时间：
2016-08
期刊：
Anatomical record (Hoboken, N.J. : 2007)
影响因子：
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作者：
Badri MK;Zhang H;Ohyama Y;Venkitapathi S;Kamiya N;Takeda H;Ray M;Scott G;Tsuji T;Kunieda T;Mishina Y;Mochida Y
通讯作者：
Mochida Y
DOI：
10.1016/j.bbrc.2011.10.026
发表时间：
2011-11-11
影响因子：
3.1
作者：
Wang, Shih-Kai;Komatsu, Yoshihiro;Mishina, Yuji
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Mishina, Yuji
DOI：
10.1002/dvg.23034
发表时间：
2017-06
期刊：
Genesis (New York, N.Y. : 2000)
影响因子：
--
作者：
Chen G;Ishan M;Yang J;Kishigami S;Fukuda T;Scott G;Ray MK;Sun C;Chen SY;Komatsu Y;Mishina Y;Liu HX
通讯作者：
Liu HX