FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease.

By D. Ornitz, P. Marie. Genes & Development, 2002

924 citations recorded by the source corpus.

Over the last decade the identification of mutations in the receptors for fibroblast growth factors (FGFs) has defined essential roles for FGF signaling in both endochondral and intramembranous bone development. FGF signaling pathways are essential for the earliest stages of limb development and throughout skeletal development. In this review, we examine the role of FGF signaling in bone development and in human genetic diseases that affect bone development. We also explore what is presently known about how FGF signaling pathways interact with other major signaling pathways that regulate chondrogenesis and osteogenesis. Overview of skeletal development Skeletal elements are formed through two distinct developmental processes. Endochondral ossification gives rise to long bones that comprise the appendicular skeleton, facial bones, vertebrae, and the lateral medial clavicles. Intramembranous ossification gives rise to the flat bones that comprise the cranium and medial clavicles. Both types of ossification involve an initial condensation of mesenchyme and the eventual formation of calcified bone. However, intramembranous bone formation accomplishes this directly, whereas endochondral ossification incorporates an intermediate step in which a cartilaginous template regulates the growth and patterning of the developing skeletal element. Development of endochondral bones initiates shortly after the formation of the limb bud with the condensation of loose mesenchyme, marked by expression of type

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ce956cc17b8b92efe6c48b96b38738a899bfdddb

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. H. Kronenberg
2. Fanxin Long
3. R. Grose
4. N. Turner
5. E. Olson
6. D. Ornitz
7. Deepak Srivastava

In Molecular Biology

1. Fanxin Long
2. D. Ornitz
3. H. Kronenberg
4. R. Grose
5. N. Turner
6. Kai Yu
7. Zhonghao Liu
8. E. Olson

Citations in the corpus

• Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth (2003, background): “Vascular invasion of hypertrophic chondrocytes from the central bone collar allows formation of the metaphysis adjacent to the hypertrophic chondrocyte zone (Karsenty and Wagner, 2002; Ornitz and Marie, 2002).”
• Mechanisms underlying differential responses to FGF signaling. (2005, background): “A major role for FGF signaling has been demonstrated in embryonic development through mouse and human genetics [1–6].”
• Building strong bones: molecular regulation of the osteoblast lineage (2011, background): “Mutations in FGFRs are responsible for a large range of congenital skeletal disorders in humans (for a more detailed discussion, see Ref”
• Developmental regulation of the growth plate (2003, background): “Many of the 22 distinct FGF genes and four FGF receptor genes are expressed at every stage of endochondral bone formatio”
• Fibroblast growth factor signalling: from development to cancer (2010, background): “In humans, several gain-of-function germline mutations in the FGFRgenes result in skeletal dysplasias, with FGFR2 mutations a common cause of craniosynostosis syndromes and FGFR3 mutations common in chondrodysplasia syndromes”
• Biological Physics of the Developing Embryo (2005, neutral): “Finally, differentiated cartilage in the more mature region, proximal to the condensing cells, expresses FGFR3, which is involved in the growth control of this tissue (Ornitz and Marie, 2002).”
• Interactions between Sox9 and β-catenin control chondrocyte differentiation (2004, background): “Indian hedgehog (Ihh) and Parathyroid hormone-related peptide (Pthrp) as well as Fibroblast growth factor receptor (Fgfr) 3 signaling control the rate of chondrocyte proliferation and the transition of proliferating chondrocytes to hypertrophy (Vortkamp et al. 1996; Ornitz and Marie 2002).”