David M Ornitz

..When inappropriately expressed, some FGFs can contribute to the pathogenesis of cancer. A subset of the FGF family, expressed in adult tissue, is important for neuronal signal transduction in the central and peripheral nervous systems...

..In developing stylopod elements, FGF9 promotes chondrocyte hypertrophy at early stages and regulates vascularization of the growth plate and osteogenesis at later stages of skeletal development...

..Finally, we present evidence suggesting that coronary arteries and veins may be derived from distinct lineages...

..FGF18 thus coordinates neovascularization of the growth plate with chondrocyte and osteoblast growth and differentiation...

..We show that FGF signaling is primarily responsible for regulating mesenchymal proliferation, whereas β-catenin signaling is a required permissive factor for mesenchymal FGF signaling...

..These data demonstrate that signaling through FGFR1 in osteoblasts is necessary to maintain the balance between bone formation and remodeling through a direct effect on osteoblast maturation...

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..Together, these studies strongly suggest that myocardial cell proliferation and coronary development are genetically separable programs exemplifying one of the many potential uses of this genetic tool...

..Together, both FGF and WNT signaling pathways function to sustain mesenchymal growth and coordinate epithelial morphogenesis during the pseudoglandular stage of lung development...

..Inactivation of this signaling pathway results in fewer epicardial derived cells within the compact myocardium, decreased myocardial proliferation and a resulting smaller thin-walled heart...

..These data suggest a molecular mechanism through which FGF9 and SHH signaling coordinately control the growth and patterning of the lung capillary plexus, and regulate the temporal and spatial expression of Vegfa...

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..Taken together, the interaction of FGF and TGFbeta signaling pathways in the intestinal mesenchyme could represent novel targets for future short bowel syndrome therapies...

..These data suggest that the tlt and mlh mutations primarily affect the localization of Otop1, which interferes with its ability to interact with other proteins that are important for its cellular and biochemical function...

..Consistent with this, activation of HH signaling in the adult heart leads to an increase in coronary vessel density...

..Together, these data demonstrate that HH signaling is essential for cardiac function at the level of the coronary vasculature and caution against the use of HH antagonists in patients with prior or ongoing heart disease...

..6 expression in Purkinje neurons, and that the loss of FGF14 impairs spontaneous and repetitive firing in Purkinje neurons by altering the expression of Nav1.6 channels...

..FGFs thus constitute all or part of the epicardial signal regulating myocardial growth and differentiation...

..This study completes the mitogenesis-based comparison of receptor specificity of the entire FGF family under standard conditions and should help in interpreting and predicting in vivo biological activity...

..Impaired theta burst initiated long-term synaptic potentiation was also found in hippocampal slices from Fgf14(-/-) mice. These results suggest a role for FGF14 in certain spatial learning functions and synaptic plasticity...

..Thus, the FGF14 N-terminus is required for targeting and functional regulation of Nav channels, suggesting an important function for FGF14 alternative splicing in regulating neuronal excitability...

..These findings identify Wnt-beta-catenin signaling as a crucial upstream regulator of a Tbx1-Fgf8 signaling pathway and suggest that factors that affect Wnt-beta-catenin signaling could modify the incidence and severity of DGS...

..Finally Wnt7b is identified as a potential endogenous ligand regulating osteogenesis. These data support a model that integrates Hh and Wnt signaling in the regulation of osteoblast development...

..Knowledge of how mesenchymal FGF signaling regulates palatal shelf development may ultimately lead to pharmacological approaches to reduce cleft palate incidence in genetically predisposed humans...

..Thus, these data add to our understanding of FGF-mediated reciprocal epithelial-mesenchymal signaling...

..The viability and hearing loss in Fgf20 knockout mice suggest that FGF20 may also be a deafness-associated gene in humans...

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..These data support a model in which OTOP1 acts as a sensor of the extracellular calcium concentration near supporting cells and responds to ATP in the endolymph to increase intracellular calcium levels during otoconia mineralization...

..We further describe the mechanism by which many of these same pathways also regulate the adult coronary vasculature and their potential use in the treatment of ischemic heart disease...

..These findings identify a long-sought-after critical component of the nephron stem cell niche and hold promise for long-term culture and utilization of these progenitors in vitro...

..It also contributes to the normal elongation of primary lens fiber cells and to the survival of lens epithelial cells...

..In this review, I will focus on the role of FGF signaling in chondrocytes and osteoblasts and how FGFs regulate the growth and development of endochondral bone...

..These studies demonstrate that Otop1 has an essential and conserved role in the timing of formation and the size and shape of the developing otolith...

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..These findings suggest a novel role for FGF14 in regulating synaptic plasticity via presynaptic mechanisms by affecting the mobilization, trafficking, or docking of synaptic vesicles to presynaptic active zones...

..Although differentiation of the osteoblast lineage was not disturbed, the proliferation of osteoprogenitors and the anabolic function of mature osteoblasts were severely affected...

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..These studies identify distinct groups of FGFs that are differentially expressed and suggest active stage-specific roles for FGF signaling during the fracture repair process...

..Collectively, our studies indicate a crucial role for ALK3 in vessel remodeling, vessel integrity and endocardial cushion formation during the development of the circulation system...

..These studies demonstrated that specific glycosaminoglycans could be useful in treating ligand-dependent FGFR signaling-related diseases, such as Apert syndrome and cancer...

..We focus on two key growth factor pathways: fibroblast growth factor and Hedgehog signaling...

..Inactivation of FGFR2 has similar effects. These results indicate that FGF22 and its relatives are presynaptic organizing molecules in the mammalian brain and suggest new functions for this family of signaling molecules...

..These studies demonstrate how advanced preparatory and analytical techniques can be applied to studies of the inner ear...

..In the future, the fatigue loading approach can be used create non-displaced bone fractures in transgenic and knockout mice to study the mechanisms by which the skeleton rapidly repairs damage...

..This study establishes the first genetic model for CDH and identifies a previously unsuspected role for Slit3 in regulating the development of the diaphragm...

..Vertebrate Otop1 and its paralogues Otop2 and Otop3 define a new gene family with homology to the invertebrate Domain of Unknown Function 270 genes (DUF270; pfam03189)...

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..In a physiologic setting, these activities could direct the formation and growth of otoconia and regulate other biomineralization processes...

..Otop1 and Otop1-like paralogues, Otop2 and Otop3, define a new gene family with homology to the C. elegans and D. melanoganster DUF270 genes...

..The purpose of this study was to develop a pharmacological strategy using tyrosine kinase inhibition as a novel treatment for craniosynostotic syndromes caused by constitutive FGFR activation...

..Our study provides a framework that recognizes variation in timing of palatal morphogenesis along the AP axis that will aid in the investigation of the mechanisms regulating palatal shelf elevation...

..This review aims to integrate the known functions of extracellular signals and transcription factors that regulate development of the endochondral skeleton...

..These observations indicate that a conserved WNT-SP8-FGF8 genetic cassette is employed by both appendages for promoting outgrowth, and suggest a deep homology shared by the limb and external genitalia...

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..Together, these findings implicate FGF14 as a unique modulator of Nav channel activity in the CNS and provide a possible mechanism to explain the neurological phenotypes observed in mice and humans with mutations in Fgf14...