Tissue-specific responses to aberrant FGF signaling in complex head phenotypes.
Tissue-specific responses to aberrant FGF signaling in complex head phenotypes.
复制标题
DOI：
10.1002/dvdy.23903
复制
发表时间：
2013-01
影响因子：
2.5
通讯作者：
Richtsmeier, Joan T.
中科院分区：
文献类型：
--
作者：
Martinez-Abadias, Neus;Motch, Susan M.;Pankratz, Talia L.;Wang, Yingli;Aldridge, Kristina;Jabs, Ethylin Wang;Richtsmeier, Joan T.
成纤维细胞生长因子和受体 (FGF/FGFR) 信号在骨骼发育中的作用已得到充分研究，部分原因是 FGFR 突变会导致人类软骨发育不全疾病和 FGFR 相关颅缝早闭综合征（包括克鲁松综合征）。 FGFR2c C342Y 突变是克鲁松综合征的常见原因，其特征是颅顶缝过早闭合、面中部缺陷和神经颅畸形。在这里，我们使用新生的 Fgfr2cC342Y/+ 克鲁宗综合征小鼠，测试了这种突变的表型效应是否超出了颅骨的骨骼组织，改变了其他非骨骼头部组织的发育，包括大脑、眼睛、鼻咽和内耳。 3D 多模态成像（高分辨率显微计算机断层扫描和磁共振显微图像）的定量分析显示，Fgfr2cC342Y/+ 小鼠与未受影响的同窝小鼠之间，颅骨形态和冠状缝通畅性存在局部差异，并且 Fgfr2cC342Y/+ 小鼠的大脑形状发生变化，但大脑大小没有变化，鼻咽和眼睛体积显着减小，内耳体积没有差异。这些发现提供了由异常 FGF/FGFR 信号传导引起的克鲁松综合征临床表型的扩展目录，并提供了 FGF/FGFR 信号传导在脊椎动物头部发育和进化中广泛作用的证据。
The role of fibroblast growth factor and receptor (FGF/FGFR) signaling in bone development is well studied, partly because mutations in FGFRs cause human diseases of achondroplasia and FGFR-related craniosynostosis syndromes including Crouzon syndrome. The FGFR2c C342Y mutation is a frequent cause of Crouzon syndrome, characterized by premature cranial vault suture closure, midfacial deficiency and neurocranial dysmorphology. Here, using newborn Fgfr2cC342Y/+ Crouzon syndrome mice, we tested whether the phenotypic effects of this mutation go beyond the skeletal tissues of the skull, altering the development of other non-skeletal head tissues including the brain, the eyes, the nasopharynx and the inner ears. Quantitative analysis of 3D multimodal imaging (high resolution micro computed tomography and magnetic resonance microscopic images) revealed local differences in skull morphology and coronal suture patency between Fgfr2cC342Y/+ mice and unaffected littermates, as well as changes in brain shape but not brain size, significant reductions in nasopharyngeal and eye volumes, and no difference in inner ear volume in Fgfr2cC342Y/+ mice. These findings provide an expanded catalogue of clinical phenotypes in Crouzon syndrome caused by aberrant FGF/FGFR signaling and evidence of the broad role for FGF/FGFR signaling in development and evolution of the vertebrate head.
登录
查看更多内容
DOI：
10.1073/pnas.1014235108
发表时间：
2011-05-31
影响因子：
11.1
作者：
Bertrand, Stephanie;Camasses, Alain;Escriva, Hector
通讯作者：
Escriva, Hector
影响因子：
4.6
作者：
Abzhanov, Arhat;Rodda, Stephen J.;Tabin, Clifford J.
通讯作者：
Tabin, Clifford J.
DOI：
10.1098/rspb.2007.1169
发表时间：
2008-01-07
影响因子：
4.7
作者：
Drake, Abby Grace;Klingenberg, Christian Peter
通讯作者：
Klingenberg, Christian Peter
影响因子：
3.7
作者：
Martínez-Abadías N;Heuzé Y;Wang Y;Jabs EW;Aldridge K;Richtsmeier JT
通讯作者：
Richtsmeier JT
影响因子：
2.7
作者：
McBratney-Owen, B.;Iseki, S.;Morriss-Kay, G. M.
通讯作者：
Morriss-Kay, G. M.