Fibroblast growth factor 10 regulates Meckel's cartilage formation during early mandibular morphogenesis in rats

Abstract

Fibroblast growth factors (FGF) are pluripotent growth factors that play pivotal roles in the development of various organs. During mandibular organogenesis, Meckel's cartilage, teeth, and mandibular bone differentiate under the control of various FGF. In the present study, we evaluated the role of FGF10 in rat mandibular chondrogenesis and morphogenesis using mandibular organ culture and mandibular cell micromass culture systems. The overexpression of Fgf10 induced by the electroporation of an FGF10 expression vector not only altered the size and shape of Meckel's cartilage, but also upregulated the expression of the cartilage characteristic genes Col2a1 and Sox9 in a mandibular organ culture system. Meckel's cartilage was deformed, and its size was increased when Fgf10 was overexpressed in the lateral area of the mandible. Meanwhile, no effect was found when Fgf10 was overexpressed in the medial portion. In the mandibular cell micromass culture, recombinant FGF10 treatment enhanced chondrogenic differentiation and endogenous ERK (extracellular signal-regulated kinase) phosphorylation in cells derived from the lateral area of the mandible. On the other hand, FGF10 did not have significant effects on mandibular cell proliferation. These results indicate that FGF10 regulates Meckel's cartilage formation during early mandibular morphogenesis by controlling the cell differentiation in the lateral area of the mandibular process in rats.

Mandible and Tongue Development

“…Conversely, overexpression of Fgf10 causes deformation of the MC and a significant increase in size. Fgf10 overexpression also induces upregulation of cartilage-specific genes such as Col2a1 and Sox9 in vitro (Terao et al, 2011). The function of the WNT pathway in the development of the MC is not clear.…”

How the pterosaur got its wings

“…In later stages (after stage 17), the further enlarged plagiopatagium bud merges with the posterior surface of the forelimb bud (Schumacher, ; Giannini, Goswami & Sánchez‐Villagra, ; Tokita, ). It is known that Fgf10 is necessary for 5′ Hoxd ‐dependent control of AER‐ Fgf s expression (Sheth et al ., ), regulates mammalian palatal outgrowth in interaction with SHH signalling (Lan & Jiang, ; Zhou et al ., ), regulates the size and shape of Meckel's cartilage in mammals (Terao, Takahashi & Mitani, ), and is expressed in chondrocytes and possibly regulates the growth of the limb skeleton through promoting chondrocyte proliferation (Sekine et al ., ). Interestingly, within the pterosaur brachiopatagium, muscular tissues were distributed between a dorsal layer composed of structural fibres and a ventral layer enriched by blood vessels (Unwin, ; Witton, ) (details of wing membrane muscles are given in Section ).…”

Enhanced BMP signaling prevents degeneration and leads to endochondral ossification of Meckel′s cartilage in mice

“…For example, Sox9 is required for the determination of chondrogenic lineage in axial and appendicular skeletal elements as well as CNC-derived cartilages and endochondral bones (Bi et al, 1999; Mori-Akiyama et al, 2003). In addition, a number of signaling molecules, including bone morphogenetic protein (BMP), connective tissue growth factor (CTGF), fibroblast growth factor (FGF), transforming growth factor β (TGFβ), and Wnt that are known to regulate chondrogenesis of appendicular skeletons, have also been implicated in Meckel’s cartilage development (Chai et al, 1994; Nonaka et al, 1999; Ito et al, 2002; Shimo et al, 2004; Terao et al, 2011; Zhang et al, 2011). However, unlike the fate of those mesoderm-derived cartilaginous elements and other CNC-derived cartilages such as cranial base, the majority of Meckel’s cartilage does not develop further and becomes degenerated.…”