Roles of FGF receptors in mammalian development and congenital diseases

Abstract

Four fibroblast growth factor receptors (FGFR1-4) constitute a family of transmembrane tyrosine kinases that serve as high affinity receptors for at least 22 FGF ligands. Gene targeting in mice has yielded valuable insights into the functions of this important gene family in multiple biological processes. These include mesoderm induction and patterning; cell growth, migration, and differentiation; organ formation and maintenance; neuronal differentiation and survival; wound healing; and malignant transformation. Furthermore, discoveries that mutations in three of the four receptors result in more than a dozen human congenital diseases highlight the importance of these genes in skeletal development. In this review, we will discuss recent progress on the roles of FGF receptors in mammalian development and congenital diseases, with an emphasis on signal transduction pathways.

Cellular Interactions in Lymph Node Development

“…At this moment, differentiation of mesenchymal cells into specialized cells that can initiate the formation of lymph nodes is expected, and one can assume that components involved in the specification of mesenchymal cells during the organogenesis or morphogenesis of other organs are involved here as well. As such, the platelet-derived growth factor (PDGF), fibroblast growth factor, as well as TGF␤ (super)family of growth factors, which are crucial for the differentiation of mesenchymal cells important for organogenesis during embryonic development (33)(34)(35)(36)(37), are likely to be involved in the earliest phases of lymphoid organ formation. Regarding the PDGF family of growth factors, it is noteworthy that stromal organizer cells present early in PP anlagen have been described to express both PDGFR␣ as well as PDGFR␤ (38).…”

Local application of recombinant human fibroblast growth factor‐2 on bone repair: A dose–escalation prospective trial on patients with osteotomy

“…3 In skeletal tissues, FGF-2 is accumulated in bone matrix and acts as an autocrine/paracrine factor. 4 Several genetic diseases with abnormalities in bone and cartilage formation, such as achondroplasia and thanatophoric dysplasia type II, have been shown to be due to mutations of genes for FGFs or their receptors, 5 suggesting the importance of FGFs in bone and cartilage formation. We and others have reported the anabolic effect of local and systemic administrations of FGF-2 on bone formation using several animal models including nonhuman primates.…”

FGFR-1 signaling is involved in spermiogenesis and sperm capacitation

“…The conservation of FGF/FGFR proteins throughout evolution, and the extreme phenotypes of constitutive knockout models (Coumoul and Deng, 2003;Ornitz and Itoh, 2001;Powers et al, 2000), is indicative of them having important roles during development. While a previous study has localized FGFR-1 to the haploid germ cell using immunohistochemistry (Cancilla and Risbridger, 1998), there are few data relating to the role of FGFR signaling in spermatogenesis and male fertility.…”