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A combined series of Fgf9 and Fgf18 mutant alleles identifies unique and redundant roles in skeletal development.
Dev Biol 2016; 411(1):72-84DB

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.

Authors+Show Affiliations

Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132, United States; Cancer and Developmental Biology Lab, National Cancer Institute, Frederick, MD 21701, United States; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States. Electronic address: irene.hung@hsc.utah.edu.Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132, United States.Cancer and Developmental Biology Lab, National Cancer Institute, Frederick, MD 21701, United States.Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States. Electronic address: dornitz@wustl.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26794256

Citation

Hung, Irene H., et al. "A Combined Series of Fgf9 and Fgf18 Mutant Alleles Identifies Unique and Redundant Roles in Skeletal Development." Developmental Biology, vol. 411, no. 1, 2016, pp. 72-84.
Hung IH, Schoenwolf GC, Lewandoski M, et al. A combined series of Fgf9 and Fgf18 mutant alleles identifies unique and redundant roles in skeletal development. Dev Biol. 2016;411(1):72-84.
Hung, I. H., Schoenwolf, G. C., Lewandoski, M., & Ornitz, D. M. (2016). A combined series of Fgf9 and Fgf18 mutant alleles identifies unique and redundant roles in skeletal development. Developmental Biology, 411(1), pp. 72-84. doi:10.1016/j.ydbio.2016.01.008.
Hung IH, et al. A Combined Series of Fgf9 and Fgf18 Mutant Alleles Identifies Unique and Redundant Roles in Skeletal Development. Dev Biol. 2016 Mar 1;411(1):72-84. PubMed PMID: 26794256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A combined series of Fgf9 and Fgf18 mutant alleles identifies unique and redundant roles in skeletal development. AU - Hung,Irene H, AU - Schoenwolf,Gary C, AU - Lewandoski,Mark, AU - Ornitz,David M, Y1 - 2016/01/16/ PY - 2015/08/26/received PY - 2016/01/14/revised PY - 2016/01/15/accepted PY - 2017/03/01/pmc-release PY - 2016/1/23/entrez PY - 2016/1/23/pubmed PY - 2016/8/2/medline KW - Chondrogenesis KW - FGF KW - Growth plate KW - Mouse SP - 72 EP - 84 JF - Developmental biology JO - Dev. Biol. VL - 411 IS - 1 N2 - 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. SN - 1095-564X UR - https://www.unboundmedicine.com/medline/citation/26794256/A_combined_series_of_Fgf9_and_Fgf18_mutant_alleles_identifies_unique_and_redundant_roles_in_skeletal_development_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0012-1606(15)30146-9 DB - PRIME DP - Unbound Medicine ER -