Fgfr mRNA isoforms in craniofacial bone development
Fgfr mRNA isoforms in craniofacial bone development
复制标题
DOI：
10.1016/s8756-3282(03)00163-7
复制
发表时间：
2003-07-01
期刊：
影响因子：
4.1
通讯作者：
Thesleff, I
中科院分区：
文献类型：
--
作者：
Rice, DPC;Rice, R;Thesleff, I
成纤维细胞生长因子受体(FGFRs)基因的突变被认为是导致软骨发育不良和颅缝融合的原因，这两种疾病都会导致颅面部的生长发育异常。FGFRs形成信使核糖核酸剪接异构体，每一种都具有不同的配体结合特异性和组织分布。它们赋予这些异构体特定的生物学功能。虽然已知FGFRs在小鼠发育早期的许多位置都有表达，包括头面部，但对剪接异构体在头面部骨骼发育过程中的表达知之甚少。为了解决这个问题，我们进行了一项详细的调查，以检测发育中的小鼠颅面部区域的这些基因。我们已经分析了发育中的小鼠下颌骨、头盖骨和颅底，特别是蝶枕骨联合软骨，这是颅面生长的关键中心。Fgfr1c在发育中的颅骨和下颌骨的成骨细胞中均有微弱的表达。Fgfr3b和Fgfr3c主要存在于颅底软骨和下颌骨的软骨细胞中。FGFR2b转录本主要见于下颌骨的软骨膜和颅底。Fgfr2c转录本在颅骨骨缝成骨前沿的成骨细胞分化中呈高强度表达。此外，Fgfr2c还表达于下颌骨的软骨膜和颅底。这些表达模式暗示了-b和-c亚型的不同和相似的功能。前者的例子是FGFR1转录本，它们在分布上表现出明显的差异，相互排斥。FGFR2和FGFR3的-b和-c亚型的重叠表达模式表明了类似的功能。在发育中的肌肉中发现了FGFR4的转录本。这些数据有助于解释两名患者表现出的头面部发育障碍，以及越来越多携带FGFRs/FGFRs编码基因突变的转基因小鼠。(C)2003 Elsevier Inc.保留所有权利。
Mutations in genes encoding for fibroblast growth factor receptors (FGFRs) have been identified as causes of both chondrodysplasias and craniosynostoses, both of which cause abnormalities in the growth and development of the craniofacial region. FGFRs form mRNA splicing isoforms, each with distinct ligand binding specificity and tissue distribution. These confer specific biological functions on these isoforms. Although it is known that FGFRs are expressed at numerous locations during early mouse development, including the craniofacial area, relatively little is known about the expression of the splicing isoforms during craniofacial bone development. To address this, we have performed a detailed survey to detect these genes in the developing mouse craniofacial region. We have analyzed the developing mouse mandible, calvaria, and cranial base, in particular the spheno-occipital synchondrosis, a key centre of craniofacial growth. Fgfr1c was detected weakly in osteoblastic cells in both the developing calvarial and mandibular bones. Fgfr3b and Fgfr3c were found chiefly in proliferating chondrocytes of the cranial base synchondroses and the mandibular condyle. Fgfr2b transcripts were most notably detected in the perichondria of the mandibular condyle and the cranial base. Fgfr2c transcripts were detected with high intensity in differentiating osteoblasts at the sutural osteogenic fronts of the calvarial bones. In addition, Fgfr2c was also expressed in the perichondria of the mandibular condyle and the cranial base. These expression patterns suggest both differing and similar functions for -b and -c isoforms. The former is exemplified by Fgfr1 transcripts, which show distinct differences in their distribution, being mutually exclusive. Similar functions are suggested by the overlapping expression patterns of the -b and -c isoforms of both Fgfr2 and Fgfr3. Fgfr4 transcripts were found in developing muscles. These data help to explain the disturbances in craniofacial growth exhibited by both patients and the growing number of transgenic mice carrying mutations in genes encoding FGFRs/Fgfrs. (C) 2003 Elsevier Inc. All rights reserved.