FGF/FGFR signaling coordinates skull development by modulating magnitude of morphological integration: evidence from Apert syndrome mouse models.
FGF/FGFR signaling coordinates skull development by modulating magnitude of morphological integration: evidence from Apert syndrome mouse models.
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DOI：
10.1371/journal.pone.0026425
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Richtsmeier JT
中科院分区：
文献类型：
--
作者：
Martínez-Abadías N;Heuzé Y;Wang Y;Jabs EW;Aldridge K;Richtsmeier JT
成纤维细胞生长因子和受体系统（FGF/FGFR）介导许多组织类型（例如，骨的、神经的、血管的）。在由FGFR 1 -3突变引起的那些颅缝早闭综合征中，FGF/FGFR系统中信号传导的改变导致颅骨、脑和四肢以及其他器官的畸形。由于这一分子途径在整个头部发育过程中广泛表达，我们使用近交系Apert综合征小鼠模型Fgfr 2 +/S252 W和Fgfr 2 +/P253 R及其非突变同窝出生仔在P0时，探索引起人类Apert综合征的Fgfr 2上的两个特定突变是否以及如何影响面部骨骼和脑颅之间的整合模式和水平。头骨形态整合（MI），它可以反映发育性状之间的相互作用，通过测量它们之间的统计关联的强度，进行了评估，使用的数据从microCT图像的头骨Apert综合征小鼠模型和三维几何形态测量方法。我们的研究结果表明，突变型Apert综合征小鼠与其非突变型同窝出生的小鼠具有MI的一般模式，但面部骨骼和脑颅之间和内部的整合程度增加，特别是在Fgfr 2 +/S252 W小鼠中。这表明，虽然Fgfr 2突变不会破坏颅骨MI，但FGF/FGFR信号传导是颅骨发育中的协方差生成过程，其充当调节MI强度的全局因素。由于这一通路在脊椎动物进化的早期就已进化，因此它可能在建立颅骨MI模式和协调适当的颅骨发育方面发挥了重要作用。
The fibroblast growth factor and receptor system (FGF/FGFR) mediates cell communication and pattern formation in many tissue types (e.g., osseous, nervous, vascular). In those craniosynostosis syndromes caused by FGFR1-3 mutations, alteration of signaling in the FGF/FGFR system leads to dysmorphology of the skull, brain and limbs, among other organs. Since this molecular pathway is widely expressed throughout head development, we explore whether and how two specific mutations on Fgfr2 causing Apert syndrome in humans affect the pattern and level of integration between the facial skeleton and the neurocranium using inbred Apert syndrome mouse models Fgfr2+/S252W and Fgfr2+/P253R and their non-mutant littermates at P0. Skull morphological integration (MI), which can reflect developmental interactions among traits by measuring the intensity of statistical associations among them, was assessed using data from microCT images of the skull of Apert syndrome mouse models and 3D geometric morphometric methods. Our results show that mutant Apert syndrome mice share the general pattern of MI with their non-mutant littermates, but the magnitude of integration between and within the facial skeleton and the neurocranium is increased, especially in Fgfr2+/S252W mice. This indicates that although Fgfr2 mutations do not disrupt skull MI, FGF/FGFR signaling is a covariance-generating process in skull development that acts as a global factor modulating the intensity of MI. As this pathway evolved early in vertebrate evolution, it may have played a significant role in establishing the patterns of skull MI and coordinating proper skull development.
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影响因子：
3.1
作者：
Richtsmeier, J. T.;DeLeon, V. B.
通讯作者：
DeLeon, V. B.
DOI：
10.1242/dev.037689
发表时间：
2010-11
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Dorey K;Amaya E
通讯作者：
Amaya E
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：
2.6
作者：
Hallgrimsson, Benedikt;Lieberman, Daniel E.
通讯作者：
Lieberman, Daniel E.
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