Molecular and cellular bases of syndromic craniosynostoses.
Molecular and cellular bases of syndromic craniosynostoses.
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DOI：
10.1017/s1462399403005751
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发表时间：
2003-01-29
影响因子：
6.2
通讯作者：
El Ghouzzi, Vincent
中科院分区：
文献类型：
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作者：
Bonaventure, Jacky;El Ghouzzi, Vincent
颅缝过早融合是“颅缝闭闭”临床状况的基础，这是一种常见的人类疾病，在非综合征和综合征两种形式中都有发生。综合征型颅缝闭锁亚群通常将肢体异常和面部畸形与颅骨变形联系起来。在过去的十年中，一些导致这些表型的基因已经被确定。其中，编码FGFR2的基因是成纤维细胞生长因子受体（FGFR）家族的四个成员之一，已被证明可以解释包括Apert， Pfeiffer, Crouzon， bear - stevenson和Jackson-Weiss综合征在内的几种严重疾病。另外两种FGFR1和FGFR3也可解释不同严重程度的颅缝紧闭（Pfeiffer，伴有黑棘皮病（一种恶性前皮肤病）的Crouzon和Muenke综合征）。相比之下，sae3 - chotzen综合征和颅缝闭锁（boston型）分别由Twist和muscle segment homeobox 2 （MSX2）转录因子突变引起。尽管大多数FGFR突变可能导致受体的非配体激活，从而导致信号通路的上调，但碱性螺旋-环-螺旋（bHLH）转录因子Twist的突变似乎会诱导蛋白质功能的丧失。本文将总结和讨论正常和异常颅面发育的一些细胞和分子机制，重点讨论控制膜性骨化的不同因素之间可能的相互作用。
Premature fusion of cranial sutures underlies the clinical condition of 'craniosynostosis', a common human disorder that occurs in both nonsyndromic and syndromic forms. The subgroup of syndromic craniosynostoses usually associates limb abnormalities and facial dysmorphism to skull distortion. Over the past decade, some of the genes causing these phenotypes have been identified. Among these, the gene encoding FGFR2, one of four members of the fibroblast growth factor receptor (FGFR) family, has been shown to account for several severe conditions including Apert, Pfeiffer, Crouzon, Beare-Stevenson and Jackson-Weiss syndromes. Two other FGFRs, FGFR1 and FGFR3, also account for craniosynostoses of variable severity (Pfeiffer, Crouzon with acanthosis nigricans (a pre-malignant skin disorder), and Muenke syndromes). By contrast, Saethre-Chotzen syndrome and craniosynostosis (Boston-type) arise from mutations in the Twist and muscle segment homeobox 2 (MSX2) transcription factors, respectively. Whereas most FGFR mutations are likely to cause ligand-independent activation of the receptor, leading to an upregulation of signaling pathways, mutations in the basic helix-loop-helix (bHLH) transcription factor Twist appear to induce loss of protein function. This review will summarise and discuss some of the cellular and molecular mechanisms involved in normal and abnormal craniofacial development, focusing on the possible interactions between the different factors controlling membranous ossification.