Spatio-temporal expression of FGFR 1, 2 and 3 genes during human embryo-fetal ossification.
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.
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. anne-lise.delezoide@nck.ap-hop-paris.fr
A L
AL
Delezoide
C
C
Benoist-Lasselin
L
L
Legeai-Mallet
M
M
Le Merrer
A
A
Munnich
M
M
Vekemans
J
J
Bonaventure
D001842:Bone and Bones / Q000737:chemistry / Q000196:embryology / Q000502:physiology; D002356:Cartilage / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D003393:Cranial Sutures / Q000737:chemistry / Q000196:embryology / Q000502:physiology; D004622:Embryo, Mammalian / Q000737:chemistry / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005121:Extremities / Q000196:embryology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics*; D006257:Head / Q000196:embryology / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018878:Limb Buds / Q000737:chemistry / Q000196:embryology / Q000254:growth & development; D008648:Mesoderm / Q000737:chemistry / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics*; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012886:Skull / Q000737:chemistry / Q000196:embryology / Q000502:physiology
D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3