Fibroblast growth factor （FGF）/fibroblast growth factor receptor （FGFR） signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital...Fibroblast growth factor （FGF）/fibroblast growth factor receptor （FGFR） signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital bone diseases, including chondrodysplasia syndromes, craniosynostosis syndromes and syndromes with dysregulated phosphate metabolism. FGF/FGFR signaling is also an important pathway involved in the maintenance of adult bone homeostasis. Multiple kinds of mouse models, mimicking human skeleton diseases caused by missense mutations in FGFs and FGFRs, have been established by knock-m/out and transgenic technologies. These genetically modified mice provide good models for studying the role of FGF/FGFR signaling in skeleton development and homeostasis. In this review, we summarize the mouse models of FGF signaling-related skeleton diseases and recent progresses regarding the molecular mechanisms, underlying the role of FGFs/FGFRs in the regulation of bone development and homeostasis. This review also provides a perspective view on future works to explore the roles of FGF signaling in skeletal development and homeostasis.展开更多
Thymic epithelial cells (TECs) are one of the most important components in thymic microenvironment supporting thymocyte development and maturation. TECs, composed of cortical and medullary TECs, are derived from a com...Thymic epithelial cells (TECs) are one of the most important components in thymic microenvironment supporting thymocyte development and maturation. TECs, composed of cortical and medullary TECs, are derived from a common bipotent progenitor, mediating thymocyte positive and negative selections. Multiple levels of signals including intracellular signaling networks and cell-cell interaction are required for TEC development and differentiation. Transcription factors Foxn1 and autoimmune regulator (Aire) are powerful regulators promoting TEC development and differentiation. Crosstalks with thymocytes and other stromal cells for extrinsic signals like RANKL, CD40L, lymphotoxin, fibroblast growth factor (FGF) and Wnt are also definitely required to establish a functional thymic microenvironment. In this review, we will summarize our current understanding about TEC development and differentiation, and its underlying multiple signal pathways.展开更多
Fibroblast growth factor 19 （FGF19） is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. ...Fibroblast growth factor 19 （FGF19） is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. FGF19 plays a key role in coordination of liver bile acid biosynthesis and gallbladder motility, and acts as a regulator of metabolic homeostasis, including strengthening insulin sensitivity, decreasing triglyceride concentration and reducing body weight.展开更多
基金supported by grants from the National Natural Science Foundation of China (81030036, 81270012, 81170809)Special Funds for Major State Basic Research Program of China (973 Program) (2014CB942904) +1 种基金the Committee of Science and Technology of Chongqing (CSTC 2011jjA1468)the foundation from national key laboratory (SKLZZ201017)
文摘Fibroblast growth factor （FGF）/fibroblast growth factor receptor （FGFR） signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital bone diseases, including chondrodysplasia syndromes, craniosynostosis syndromes and syndromes with dysregulated phosphate metabolism. FGF/FGFR signaling is also an important pathway involved in the maintenance of adult bone homeostasis. Multiple kinds of mouse models, mimicking human skeleton diseases caused by missense mutations in FGFs and FGFRs, have been established by knock-m/out and transgenic technologies. These genetically modified mice provide good models for studying the role of FGF/FGFR signaling in skeleton development and homeostasis. In this review, we summarize the mouse models of FGF signaling-related skeleton diseases and recent progresses regarding the molecular mechanisms, underlying the role of FGFs/FGFRs in the regulation of bone development and homeostasis. This review also provides a perspective view on future works to explore the roles of FGF signaling in skeletal development and homeostasis.
基金supported by grants from the National Basic Research Program(973 Program)(Nos.2010CB945301,and 2011CB710903,Y.Z.)National Natural Science Foundation of China(Grant Nos.C81072396 and U0832003,Y.Z.).
文摘Thymic epithelial cells (TECs) are one of the most important components in thymic microenvironment supporting thymocyte development and maturation. TECs, composed of cortical and medullary TECs, are derived from a common bipotent progenitor, mediating thymocyte positive and negative selections. Multiple levels of signals including intracellular signaling networks and cell-cell interaction are required for TEC development and differentiation. Transcription factors Foxn1 and autoimmune regulator (Aire) are powerful regulators promoting TEC development and differentiation. Crosstalks with thymocytes and other stromal cells for extrinsic signals like RANKL, CD40L, lymphotoxin, fibroblast growth factor (FGF) and Wnt are also definitely required to establish a functional thymic microenvironment. In this review, we will summarize our current understanding about TEC development and differentiation, and its underlying multiple signal pathways.
基金supported by the Major Program of the Shanghai Municipality for Basic Research(10JC1412400)the National Natural Science Foundation Major International(Regional)Joint Research Project(81220108006)
文摘Fibroblast growth factor 19 （FGF19） is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. FGF19 plays a key role in coordination of liver bile acid biosynthesis and gallbladder motility, and acts as a regulator of metabolic homeostasis, including strengthening insulin sensitivity, decreasing triglyceride concentration and reducing body weight.
