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A combined series of Fgf9 and Fgf18 mutant alleles identifies unique and redundant roles in skeletal development.
- Source :
-
Developmental biology [Dev Biol] 2016 Mar 01; Vol. 411 (1), pp. 72-84. Date of Electronic Publication: 2016 Jan 16. - Publication Year :
- 2016
-
Abstract
- Fibroblast growth factor (FGF) signaling is a critical regulator of skeletal development. Fgf9 and Fgf18 are the only FGF ligands with identified functions in embryonic bone growth. Mice lacking Fgf9 or Fgf18 have distinct skeletal phenotypes; however, the extent of overlapping or redundant functions for these ligands and the stage-specific contributions of FGF signaling to chondrogenesis and osteogenesis are not known. To identify separate versus shared roles for FGF9 and FGF18, we generated a combined series of Fgf9 and Fgf18 null alleles. Analysis of embryos lacking alleles of Fgf9 and Fgf18 shows that both encoded ligands function redundantly to control all stages of skeletogenesis; however, they have variable potencies along the proximodistal limb axis, suggesting gradients of activity during formation of the appendicular skeleton. Congenital absence of both Fgf9 and Fgf18 results in a striking osteochondrodysplasia and revealed functions for FGF signaling in early proximal limb chondrogenesis. Additional defects were also noted in craniofacial bones, vertebrae, and ribs. Loss of alleles of Fgf9 and Fgf18 also affect the expression of genes encoding other key intrinsic skeletal regulators, including IHH, PTHLH (PTHrP), and RUNX2, revealing potential direct, indirect, and compensatory mechanisms to coordinate chondrogenesis and osteogenesis.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Bone and Bones abnormalities
Cell Differentiation
Chondrocytes metabolism
Core Binding Factor Alpha 1 Subunit biosynthesis
Fibroblast Growth Factor 9 genetics
Fibroblast Growth Factors genetics
Growth Plate embryology
Hedgehog Proteins biosynthesis
Mice
Mice, Knockout
Parathyroid Hormone-Related Protein biosynthesis
Signal Transduction genetics
Bone Development genetics
Bone and Bones embryology
Chondrogenesis genetics
Fibroblast Growth Factor 9 physiology
Fibroblast Growth Factors physiology
Osteochondrodysplasias genetics
Osteogenesis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1095-564X
- Volume :
- 411
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Developmental biology
- Publication Type :
- Academic Journal
- Accession number :
- 26794256
- Full Text :
- https://doi.org/10.1016/j.ydbio.2016.01.008