Nobuyuki Itoh

..Although most Fgfs act in development in a paracrine and/or autocrine manner, some have potential roles in metabolism in an endocrine manner. In humans, Fgf signaling disorders result in hereditary diseases and cancers...

..During metazoan evolution, the Fgf family expanded in two phases, after the separation of protostomes and deuterostomes and in the evolution of early vertebrates. These expansions enabled FGFs to acquire diverse actions and functions...

..These findings indicate the importance of FGF20 for the differentiation and survival of dopaminergic neurons and the etiology and therapy of Parkinson's disease...

..Fgf10 also induces the differentiation of embryonic stem cells into a gut-like structure, cardiomyocytes, and hepatocytes. These findings indicate the crucial roles of Fgf10 in development, disease, and regenerative medicine. ..

..Serum FGF21 levels are increased in patients with metabolic diseases having insulin resistance, indicating that FGF21 is a metabolic regulator and a biomarker for these diseases...

..As the zebrafish system has proved useful for studying gene functions and genetic diseases, the present findings will be useful for elucidation of roles of FGFs in zebrafish and humans...

..During the evolution of early vertebrates, the Fgf subfamilies further expanded to contain three or four members in each subfamily...

..In addition, serum Fgf19 or Fgf21 levels are significantly increased by metabolic disorders. Hormone-like Fgfs are newly emerging and quite unique in their evolution and function...

..The expansion of the Fgf and Fgfr gene families has enabled this signaling system to acquire functional diversity and, therefore, an almost ubiquitous involvement in developmental and physiological processes...

..The inhibition of Brorin-like functions in zebrafish resulted in the impairment of neural development. Brorin-like potentially plays roles in neural development and functions...

..Knockdown of Fgf19 also caused incorrect axon pathfinding. The present findings indicate that Fgf19 positively regulates the patterning and growth of the retina, and the differentiation and growth of the lens in zebrafish...

..Furthermore, fgf22 partially rescued the fgf3/fgf8 double morphant phenotype. The present results indicate Fgf22 to be involved in midbrain development downstream of Fgf3 and Fgf8 in the MHB but not of Hh in the floor plate. ..

..The expression profile and activity indicate that neudesin plays unique roles in neural development. The present findings have revealed new potential roles of neudesin in neural cell proliferation and neuronal differentiation...

..Brorin protein promoted neurogenesis, but not astrogenesis, in mouse neural precursor cells. The present findings indicate that Brorin is a novel secreted BMP antagonist that potentially plays roles in neural development and functions...

..The present findings indicate that Fgf4 plays a unique role in the LR patterning of visceral organs in zebrafish...

..Neucrin is a unique secreted Wnt antagonist that is predominantly expressed in developing neural tissues and plays roles in neural development in zebrafish...

..As hepatic Fgf21 expression was markedly induced in mice fed KD, we examined the effects of KD feeding on metabolism and the roles of Fgf21 in metabolism in mice fed KD using Fgf21 knockout mice...

..The present findings have revealed a novel secreted lateral plate mesoderm signal essential for fin initiation in the lateral plate mesoderm...

..FGF21 may be a "thrifty factor". Serum FGF21 levels are increased in patients with metabolic diseases related with obesity, indicating potential roles of FGF21 in adipocyte metabolism...

..The cell proliferation during the terminal saccular stage stimulated by Fgf18 might play roles in the remodeling of the distal lung...

..The identification of neudesin, a novel secreted protein with a unique primary structure and neurotrophic activity, will provide new insights into the development and maintenance of neuron..

..In contrast, expression but not phosphorylation of pRb was impaired in the Fgf10(-/-) WAT. As pRb is essential for adipogenesis, Fgf10 might play a role in adipogenesis by inducing its expression...

..The embryonic heart phenotype is similar to that of the Fgf9 knockout heart, indicating Fgf9 and Fgf16 to synergistically act as growth factors for embryonic cardiomyocytes...

..The present results indicate that Fgf21 regulates lipolysis in adipocytes in response to the metabolic state but is not required for ketogenesis and triglyceride clearance in the liver...

..These findings have revealed that Fgf16, a newly identified AER factor, plays a crucial role in pectoral fin bud outgrowth by mediating the interactions of AER-mesenchyme and AER-ZPA...

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..In this review, we summarize the identification, structure, and bioactivity of members of the MAPR family, and present an essential overview of the current understanding of their physiological roles...

..Fgfr1 knockdown embryos also showed dysplastic neurocranial and pharyngeal cartilages. The present findings indicate that Fgf20b is required for ectomesenchymal fate establishment via the activation of Fgfr1 in zebrafish...

..The present findings indicate that Fgf19 signaling is crucial for forebrain development by interacting with Hh and provide new insights into the roles of Fgf signaling in brain development...

..The present findings indicate that the activation of the MAPK pathway by FGF-20 signaling through FGFR-1c plays important roles in the survival of dopaminergic neurons in the SNPC...

..Unexpectedly, the transcriptional cascade of adipogenesis in vivo described here is distinct from the cascade in vitro previously reported...

..These results indicate that Fgf21 is a newly identified factor essential for the determination of myelo-erythroid progenitor cell fate in vivo...

..Unlike in normal teeth, excess BMP accelerates patterning in ectodin-deficient teeth. We propose that ectodin is critical for robust spatial delineation of enamel knots and cusps...

..The present findings should provide new insights into the roles of Fgf signaling in cardiac remodeling...

..The expression pattern of Neucrin is distinct from that of any Dkk. Neucrin is a unique secreted Wnt antagonist that is predominantly expressed in developing neural tissues...

..FGF-18 was found to have no neurotrophic activity. The present findings indicated that FGF-18 is a unique FGF that plays a role as a neuron-derived glial cell growth factor in early postnatal development when gliogenesis occurs...

..Our findings indicate that sclerostin plays an important role in bone remodeling and links bone resorption and bone apposition...

..The results of the present study indicate that Fgf16 signaling, which is regulated by the downstream pathways of Hh-Fgf19 in the forebrain, is involved in forebrain development. ..

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..These findings suggest that neudesin plays a critical role in the early stage of adipocyte differentiation in which C/EBPbeta induces PPARgamma and C/EBPalpha expressions, by controlling the MAPK pathway...

..The brain-specific expression of pt-GalNAc-T suggested its involvement in brain development, through O-glycosylation of proteins in the neurons...

..Inhibitors of the MAPK pathway, PD98059 and SB203580, also blocked the activity of FGF-23. The present findings have revealed a novel MAPK-dependent mechanism of the regulation of phosphate uptake by FGF signaling...

..Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons and attenuated MPTP-induced neurological symptoms...

..Conversely, chondrocyte proliferation and the number of differentiated chondrocytes are increased. Therefore, FGF18 appears to regulate cell proliferation and differentiation positively in osteogenesis and negatively in chondrogenesis...

..All these effects of FGF-18 bore a close resemblance to those of FGF-2, whereas FGF-10 affects none of these cells. FGF-18 may therefore compensate for the action of FGF-2 on bone and cartilage...

..Therefore, FGF10 plays an important role in adipogenesis, at least partly by contributing to the expression of C/EBPbeta through an autocrine/paracrine mechanism...

..However, recombinant human FGF10 protein rescued the cervical loop from apoptosis. Taken together, these results suggest that FGF10 is a survival factor that maintains the stem cell population in developing incisor germs...

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..Our results also suggest that FGF signaling is involved in the maintenance of mammary bud 4, and that Fgf10 deficient epithelium can undergo branching morphogenesis into the mammary fat pad precursor...

..Hair follicle marker genes such as Sonic hedgehog, Patched, and Patched 2 are aberrantly expressed in the mutant whiskers. Thus, FGF10 is required for proper whisker development mediated by SHH signaling in the mouse...

..Effects were unique to FGF-18 because expression of other members of the FGF family had different consequences. These data show that FGF-18 is capable of enhancing proximal and inhibiting peripheral programs during lung morphogenesis...

..We conclude that Lunatic fringe may play a role in boundary formation of the enamel knot and that Notch-signaling in the dental epithelium is regulated by mesenchymal FGFs and BMP...

..These findings suggest the possibility of CS-E being a binding partner, a coreceptor, or a genuine receptor for various Hep-binding growth factors in the brain and possibly also in other tissues...

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..Thus, the library may provide new reagents to specifically regulate bindings of the growth factors to HS...

..We suggest that elevated AS mutant FGFR2b signaling may account for the dermatological manifestations of AS...

..Our results may explain one of the molecular mechanisms of the growth stimulating action of CNP and suggest that activation of the CNP/GC-B pathway may be effective as a novel therapeutic strategy for achondroplasia...