Unravelling the molecular control of calvarial suture fusion in children with craniosynostosis.
Unravelling the molecular control of calvarial suture fusion in children with craniosynostosis.
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DOI：
10.1186/1471-2164-8-458
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发表时间：
2007-12-12
期刊：
影响因子：
4.4
通讯作者：
Powell BC
中科院分区：
文献类型：
--
作者：
Coussens AK;Wilkinson CR;Hughes IP;Morris CP;van Daal A;Anderson PJ;Powell BC
颅缝早闭，即颅缝过早融合，是一种常见的颅面畸形。已经确定了10多个基因的致病突变，涉及成纤维细胞生长因子，转化生长因子β和Eph/ephrin信号通路。突变影响每个人的颅骨缝（冠状，矢状，额颞，和齿状突）不同，这表明不同的基因表达模式存在于每个人的缝。为了更好地了解人类骨缝形态发生的分子调控，我们使用微阵列分析来鉴定颅缝早闭患儿骨缝融合过程中差异表达的基因。还分析了每种未融合缝线类型之间、综合征型和非综合征型颅缝早闭患者的缝线之间以及患有和不患有颅缝早闭的个体的未融合缝线之间的表达差异。我们确定了与融合/融合缝线相比，未融合缝线中表达增加的基因，这些基因可能对维持缝线通畅性或控制早期成骨细胞分化至关重要（即RBP 4、GPC 3、C1 QTNF 3、IL 11 RA、PTN、POT）。此外，我们已经鉴定了在融合/融合的缝合组织中表达增加的基因，我们认为这些基因可能在过早的缝合融合中起作用（即WIF 1、ANXA 3、CYFIP 2）。这些基因中的两个，磷脂酰肌醇蛋白聚糖3和视黄醇结合蛋白4，蛋白质进行了研究，通过免疫组织化学和本地化的缝间充质和成骨细胞的发展中的人类颅盖骨，分别提示这些蛋白质的新角色，在维持缝合通畅性或在控制早期成骨细胞分化。我们发现，从综合征型和非综合征型颅缝早闭患者分离的缝线之间的全基因组表达差异有限，并通过定量RT-PCR证实了这一点。此外，注意到每种未融合缝线类型的不同表达谱，其中额位缝线最不相同。最后，虽然颅骨通常被认为没有软骨前体的生长，我们显示组织学和软骨特异性基因表达的识别，软骨可能参与的形态发生？这项研究提供了进一步了解复杂的信号网络，控制人类颅缝形态发生和颅缝早闭。已鉴定的基因是靶向治疗开发和筛选导致颅缝早闭突变的候选基因。
Craniosynostosis, the premature fusion of calvarial sutures, is a common craniofacial abnormality. Causative mutations in more than 10 genes have been identified, involving fibroblast growth factor, transforming growth factor beta, and Eph/ephrin signalling pathways. Mutations affect each human calvarial suture (coronal, sagittal, metopic, and lambdoid) differently, suggesting different gene expression patterns exist in each human suture. To better understand the molecular control of human suture morphogenesis we used microarray analysis to identify genes differentially expressed during suture fusion in children with craniosynostosis. Expression differences were also analysed between each unfused suture type, between sutures from syndromic and non-syndromic craniosynostosis patients, and between unfused sutures from individuals with and without craniosynostosis. We identified genes with increased expression in unfused sutures compared to fusing/fused sutures that may be pivotal to the maintenance of suture patency or in controlling early osteoblast differentiation (i.e. RBP4, GPC3, C1QTNF3, IL11RA, PTN, POSTN). In addition, we have identified genes with increased expression in fusing/fused suture tissue that we suggest could have a role in premature suture fusion (i.e. WIF1, ANXA3, CYFIP2). Proteins of two of these genes, glypican 3 and retinol binding protein 4, were investigated by immunohistochemistry and localised to the suture mesenchyme and osteogenic fronts of developing human calvaria, respectively, suggesting novel roles for these proteins in the maintenance of suture patency or in controlling early osteoblast differentiation. We show that there is limited difference in whole genome expression between sutures isolated from patients with syndromic and non-syndromic craniosynostosis and confirmed this by quantitative RT-PCR. Furthermore, distinct expression profiles for each unfused suture type were noted, with the metopic suture being most disparate. Finally, although calvarial bones are generally thought to grow without a cartilage precursor, we show histologically and by identification of cartilage-specific gene expression that cartilage may be involved in the morphogenesis of lambdoid and posterior sagittal sutures. This study has provided further insight into the complex signalling network which controls human calvarial suture morphogenesis and craniosynostosis. Identified genes are candidates for targeted therapeutic development and to screen for craniosynostosis-causing mutations.
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DOI：
10.1083/jcb.200106147
发表时间：
2001-12-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jiménez MJ;Balbín M;Alvarez J;Komori T;Bianco P;Holmbeck K;Birkedal-Hansen H;López JM;López-Otín C
通讯作者：
López-Otín C
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
0.9
作者：
Anderson, Peter J.;Netherway, David J.;Self, Peter
通讯作者：
Self, Peter
影响因子：
3.6
作者：
Bradley, JP;Han, VKM;Longaker, MT
通讯作者：
Longaker, MT
影响因子：
4.8
作者：
Kawashima-Ohya, Y;Kurata, Y;Kato, Y
通讯作者：
Kato, Y