Delezoide A L, Benoist-Lasselin C, Legeai-Mallet L, Le Merrer M, Munnich A, Vekemans M, Bonaventure J
INSERM U 393 and Département de Génétique, Assistance Publique - Hôpitaux de Paris, Groupe Hospitalier Necker Enfants Malades, 149 rue de Sèvres, 75743, Paris Cedex 15, France.
Mech Dev. 1998 Sep;77(1):19-30. doi: 10.1016/s0925-4773(98)00133-6.
Mutations in FGFR 1-3 genes account for various human craniosynostosis syndromes, while dwarfism syndromes have been ascribed exclusively to FGFR 3 mutations. However, the exact role of FGFR 1-3 genes in human skeletal development is not understood. Here we describe the expression pattern of FGFR 1-3 genes during human embryonic and fetal endochondral and membranous ossification. In the limb bud, FGFR 1 and FGFR 2 are initially expressed in the mesenchyme and in epidermal cells, respectively, but FGFR 3 is undetectable. At later stages, FGFR 2 appears as the first marker of prechondrogenic condensations. In the growing long bones, FGFR 1 and FGFR 2 transcripts are restricted to the perichondrium and periosteum, while FGFR 3 is mainly expressed in mature chondrocytes of the cartilage growth plate. Marked FGFR 2 expression is also observed in the periarticular cartilage. Finally, membranous ossification of the skull vault is characterized by co-expression of the FGFR 1-3 genes in preosteoblasts and osteoblasts. In summary, the simultaneous expression of FGFR 1-3 genes in cranial sutures might explain their involvement in craniosynostosis syndromes, whereas the specific expression of FGFR 3 in chondrocytes does correlate with the involvement of FGFR 3 mutations in inherited defective growth of human long bones.
FGFR 1 - 3基因的突变导致了多种人类颅缝早闭综合征，而侏儒症综合征则完全归因于FGFR 3突变。然而，FGFR 1 - 3基因在人类骨骼发育中的确切作用尚不清楚。在此，我们描述了FGFR 1 - 3基因在人类胚胎及胎儿软骨内成骨和膜内成骨过程中的表达模式。在肢芽中，FGFR 1和FGFR 2最初分别在间充质和表皮细胞中表达，但未检测到FGFR 3。在后期，FGFR 2成为软骨前凝聚的首个标志物。在生长中的长骨中，FGFR 1和FGFR 2转录本局限于软骨膜和骨膜，而FGFR 3主要在软骨生长板的成熟软骨细胞中表达。在关节周围软骨中也观察到显著的FGFR 2表达。最后，颅顶的膜内成骨特征是FGFR 1 - 3基因在前成骨细胞和成骨细胞中共同表达。总之，FGFR 1 - 3基因在颅缝中的同时表达可能解释了它们与颅缝早闭综合征的关联，而FGFR 3在软骨细胞中的特异性表达确实与FGFR 3突变在人类长骨遗传性生长缺陷中的作用相关。
