Genomes and Genes
Gene Symbol: Fgf14
Description: fibroblast growth factor 14
Alias: FHF-4, Fhf4, Tg(tetO-MAPT*P301L)4510Kha, mFHF-4(1B), fibroblast growth factor 14, FGF-14, fibroblast growth factor homologous factor 4
- Spires T, Orne J, Santacruz K, Pitstick R, Carlson G, Ashe K, et al. Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy. Am J Pathol. 2006;168:1598-607 pubmed..Together, these results imply that neurofibrillary tangles do not necessarily lead to neuronal death. ..
- Ljungberg M, Ali Y, Zhu J, Wu C, Oka K, Zhai R, et al. CREB-activity and nmnat2 transcription are down-regulated prior to neurodegeneration, while NMNAT2 over-expression is neuroprotective, in a mouse model of human tauopathy. Hum Mol Genet. 2012;21:251-67 pubmed publisher..Decreased endogenous NMNAT2 function caused by reduced CREB signaling during pathological insults may be one of underlying mechanisms for neuronal death in tauopathies. ..
- Rocher A, Crimins J, Amatrudo J, Kinson M, Todd Brown M, Lewis J, et al. Structural and functional changes in tau mutant mice neurons are not linked to the presence of NFTs. Exp Neurol. 2010;223:385-93 pubmed publisher..Our observations show that expression of mutated tau results in significant structural and functional changes in neurons, but that these changes occur independent of mature NFT formation...
- Abisambra J, Jinwal U, Blair L, O Leary J, Li Q, Brady S, et al. Tau accumulation activates the unfolded protein response by impairing endoplasmic reticulum-associated degradation. J Neurosci. 2013;33:9498-507 pubmed publisher..The reversibility of this process, however, suggests that tau-based therapeutics could significantly delay this type of cell death and therefore disease progression...
- Wang Q, McEwen D, Ornitz D. Subcellular and developmental expression of alternatively spliced forms of fibroblast growth factor 14. Mech Dev. 2000;90:283-7 pubmed..Here we characterize two isoforms of FGF14 (FGF14-1a and FGF14-1b) that result from the alternative usage of two different first exons...
- Shakkottai V, Xiao M, Xu L, Wong M, Nerbonne J, Ornitz D, et al. FGF14 regulates the intrinsic excitability of cerebellar Purkinje neurons. Neurobiol Dis. 2009;33:81-8 pubmed publisherA missense mutation in the fibroblast growth factor 14 (FGF14) gene underlies SCA27, an autosomal dominant spinocerebellar ataxia in humans...
- Yue M, Hanna A, Wilson J, Roder H, Janus C. Sex difference in pathology and memory decline in rTg4510 mouse model of tauopathy. Neurobiol Aging. 2011;32:590-603 pubmed publisher..These findings suggest that the onset of abnormal tau biochemistry and coincident cognitive deficits in the rTg4510 mouse model is sex-dependent with females being affected earlier and more aggressively than males. ..
- Xiao M, Bosch M, Nerbonne J, Ornitz D. FGF14 localization and organization of the axon initial segment. Mol Cell Neurosci. 2013;56:393-403 pubmed publisher..We previously reported that FGF14, a member of the intracellular FGF (iFGF) sub-family, is expressed in cerebellar Purkinje neurons and that the ..
- SantaCruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, et al. Tau suppression in a neurodegenerative mouse model improves memory function. Science. 2005;309:476-81 pubmed..Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy. ..
- Wang Q, Bardgett M, Wong M, Wozniak D, Lou J, McNeil B, et al. Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14. Neuron. 2002;35:25-38 pubmedb>Fibroblast growth factor 14 (FGF14) belongs to a distinct subclass of FGFs that is expressed in the developing and adult CNS...
- Takeda S, Wegmann S, Cho H, DeVos S, Commins C, Roe A, et al. Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain. Nat Commun. 2015;6:8490 pubmed publisher..Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development. ..
- Shavkunov A, Wildburger N, Nenov M, James T, Buzhdygan T, Panova Elektronova N, et al. The fibroblast growth factor 14·voltage-gated sodium channel complex is a new target of glycogen synthase kinase 3 (GSK3). J Biol Chem. 2013;288:19370-85 pubmed publisherThe FGF14 protein controls biophysical properties and subcellular distribution of neuronal voltage-gated Na(+) (Nav) channels through direct binding to the channel C terminus...
- Koppel J, Jimenez H, Azose M, d Abramo C, Acker C, Buthorn J, et al. Pathogenic tau species drive a psychosis-like phenotype in a mouse model of Alzheimer's disease. Behav Brain Res. 2014;275:27-33 pubmed publisher..This preliminary data suggests the utility of the rTg4510 mouse as a candidate disease model of human female AD+P. Further work expanded to include both genders and other behavioral outcome measures relevant to AD+P is necessary. ..
- Du W, Prochazka J, Prochazkova M, Klein O. Expression of FGFs during early mouse tongue development. Gene Expr Patterns. 2016;20:81-7 pubmed publisher..Our results indicate that FGF signaling regulates tongue development at multiple stages. ..
- Wegmann S, Maury E, Kirk M, Saqran L, Roe A, DeVos S, et al. Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity. EMBO J. 2015;34:3028-41 pubmed publisher..Therefore, misfolded tau can propagate across neural systems without requisite templated misfolding, but the absence of endogenous tau markedly blunts toxicity. These results show that tau does not strictly classify as a prion protein. ..
- Holmes H, Colgan N, Ismail O, Ma D, Powell N, O Callaghan J, et al. Imaging the accumulation and suppression of tau pathology using multiparametric MRI. Neurobiol Aging. 2016;39:184-94 pubmed publisher..We propose that these non-invasive MRI techniques offer insight into pathologic mechanisms underpinning Alzheimer's disease that may be important when evaluating emerging therapeutics targeting one of more of these processes. ..
- Nobuhara C, DeVos S, Commins C, Wegmann S, Moore B, Roe A, et al. Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro. Am J Pathol. 2017;187:1399-1412 pubmed publisher..Furthermore, 6C5 slowed down the progression of tau aggregation even after uptake had begun. Our results imply that not all antibodies/epitopes are equally robust in terms of blocking tau uptake of human AD-derived tau species. ..
- Shelton L, Baker J, Zheng D, Sullivan L, Solanki P, Webster J, et al. Hsp90 activator Aha1 drives production of pathological tau aggregates. Proc Natl Acad Sci U S A. 2017;114:9707-9712 pubmed publisher..This suggests that therapeutics targeting Aha1 may reduce toxic tau oligomers and slow or prevent neurodegenerative disease progression. ..
- Cook C, Carlomagno Y, Gendron T, Dunmore J, Scheffel K, Stetler C, et al. Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance. Hum Mol Genet. 2014;23:104-16 pubmed publisher..As such, we have uncovered a novel therapeutic pathway that can be manipulated to block the formation of pathogenic tau species in disease. ..
- Sherman M, LaCroix M, Amar F, Larson M, Forster C, Aguzzi A, et al. Soluble Conformers of Aβ and Tau Alter Selective Proteins Governing Axonal Transport. J Neurosci. 2016;36:9647-58 pubmed publisher..Our findings suggest that Aβ trimers might cause axonal transport deficits in AD. ..
- Ward S, Himmelstein D, Ren Y, Fu Y, Yu X, Roberts K, et al. TOC1: a valuable tool in assessing disease progression in the rTg4510 mouse model of tauopathy. Neurobiol Dis. 2014;67:37-48 pubmed publisher..With the help of other novel antibodies, the use of this antibody will aid in providing a better understanding of tau toxicity within Alzheimer's disease and other tauopathies. ..
- Pablo J, Wang C, Presby M, Pitt G. Polarized localization of voltage-gated Na+ channels is regulated by concerted FGF13 and FGF14 action. Proc Natl Acad Sci U S A. 2016;113:E2665-74 pubmed publisher..In contrast, homologous FGF14, which is highly concentrated in the proximal axon, binds directly to VGSCs to promote their axonal localization...
- Dover K, Marra C, Solinas S, Popovic M, Subramaniyam S, Zecevic D, et al. FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon. Nat Commun. 2016;7:12895 pubmed publisher..The absence of FHFs from Navs at nodes of Ranvier in the central nervous system suggests a similar mechanism of current flux minimization along myelinated axons. ..
- Hu X, Cheng X, Cai L, Tan G, Xu L, Feng X, et al. Conditional deletion of NRSF in forebrain neurons accelerates epileptogenesis in the kindling model. Cereb Cortex. 2011;21:2158-65 pubmed publisher..The degree of upregulation of Fibroblast growth factor 14 and Brain-derived neurotrophic factor (BDNF) following kainic acid-induced status epilepticus was ..
- Jackson J, Witton J, Johnson J, Ahmed Z, Ward M, Randall A, et al. Altered Synapse Stability in the Early Stages of Tauopathy. Cell Rep. 2017;18:3063-3068 pubmed publisher..This imbalance between pre- and post-synaptic stability coincides with reduced synaptically driven neuronal activity in pre-degenerative stages of the disease. ..
- Sahara N, Pérez P, Lin W, Dickson D, Ren Y, Zeng H, et al. Age-related decline in white matter integrity in a mouse model of tauopathy: an in vivo diffusion tensor magnetic resonance imaging study. Neurobiol Aging. 2014;35:1364-74 pubmed publisher..Further in vivo DT-MRI studies in the rTg4510 mouse should help better discern the detailed mechanisms of reduced FA and anisotropy mode, and the specific role of tau during neurodegeneration. ..
- Hunsberger H, Rudy C, Batten S, Gerhardt G, Reed M. P301L tau expression affects glutamate release and clearance in the hippocampal trisynaptic pathway. J Neurochem. 2015;132:169-82 pubmed publisher..P301L tau expression increases vGLUT expression and glutamate release, while also decreasing GLT-1 expression and glutamate clearance. ..
- Alshammari T, Alshammari M, Nenov M, Hoxha E, Cambiaghi M, Marcinno A, et al. Genetic deletion of fibroblast growth factor 14 recapitulates phenotypic alterations underlying cognitive impairment associated with schizophrenia. Transl Psychiatry. 2016;6:e806 pubmed publisher..Here we show that in animal models, genetic deletion of fibroblast growth factor 14 (Fgf14), a regulator of neuronal excitability and synaptic transmission, leads to loss of PV ..
- Maeda S, Djukic B, Taneja P, Yu G, Lo I, Davis A, et al. Expression of A152T human tau causes age-dependent neuronal dysfunction and loss in transgenic mice. EMBO Rep. 2016;17:530-51 pubmed publisher..Thus, the A152T substitution may augment risk for neurodegenerative diseases by increasing hTau protein levels, promoting network hyperexcitability, and synergizing with the adverse effects of other pathogenic factors. ..
- Larson M, Sherman M, Greimel S, Kuskowski M, Schneider J, Bennett D, et al. Soluble ?-synuclein is a novel modulator of Alzheimer's disease pathophysiology. J Neurosci. 2012;32:10253-66 pubmed publisher..Altogether, our data reveal an unexpected role for soluble, intraneuronal ?Syn in AD pathophysiology. ..
- Scott L, Kiss T, Kawabe T, HajÃ³s M. Neuronal network activity in the hippocampus of tau transgenic (Tg4510) mice. Neurobiol Aging. 2016;37:66-73 pubmed publisher..However, the remaining synapses and neuronal circuitry seem to function properly in these assays. ..
- Hunsberger H, Weitzner D, Rudy C, Hickman J, Libell E, Speer R, et al. Riluzole rescues glutamate alterations, cognitive deficits, and tau pathology associated with P301L tau expression. J Neurochem. 2015;135:381-94 pubmed publisher..These findings open new opportunities for the development of clinically applicable therapeutic approaches to regulate glutamate in vulnerable circuits for those at risk for the development of AD. ..
- DUBOFF B, Götz J, Feany M. Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron. 2012;75:618-32 pubmed publisher..Our results thus identify actin-mediated disruption of mitochondrial dynamics as a direct mechanism of tau toxicity in neurons in vivo...
- Polito V, Li H, Martini Stoica H, Wang B, Yang L, Xu Y, et al. Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol Med. 2014;6:1142-60 pubmed publisher..The specificity and efficacy of TFEB in mediating the clearance of toxic Tau species makes it an attractive therapeutic target for treating diseases of tauopathy including AD. ..
- Ciupek S, Cheng J, Ali Y, Lu H, Ji D. Progressive functional impairments of hippocampal neurons in a tauopathy mouse model. J Neurosci. 2015;35:8118-31 pubmed publisher..The results reveal a tau-pathology-induced progression of hippocampal functional changes in vivo. ..
- Zhao X, Kotilinek L, Smith B, Hlynialuk C, ZAHS K, Ramsden M, et al. Caspase-2 cleavage of tau reversibly impairs memory. Nat Med. 2016;22:1268-1276 pubmed publisher..Our results suggest an overall treatment strategy for re-establishing synaptic function and restoring memory in patients with AD by preventing tau from accumulating in dendritic spines. ..
- Zhou Y, Hayashi I, Wong J, Tugusheva K, Renger J, Zerbinatti C. Intracellular clusterin interacts with brain isoforms of the bridging integrator 1 and with the microtubule-associated protein Tau in Alzheimer's disease. PLoS ONE. 2014;9:e103187 pubmed publisher..Together, our findings suggest that iCLU and BIN1 interaction might impact Tau function in neurons and uncover potential new mechanisms underlying the etiology of Tau pathology in AD. ..
- Myeku N, CLELLAND C, Emrani S, Kukushkin N, Yu W, Goldberg A, et al. Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling. Nat Med. 2016;22:46-53 pubmed publisher..In vivo, this led to lower levels of aggregated tau and improvements in cognitive performance. ..
- Fontaine S, Ingram A, Cloyd R, Meier S, Miller E, Lyons D, et al. Identification of changes in neuronal function as a consequence of aging and tauopathic neurodegeneration using a novel and sensitive magnetic resonance imaging approach. Neurobiol Aging. 2017;56:78-86 pubmed publisher..Successful translation of this technology in the clinic could serve as a sensitive diagnostic tool for the definition of effective therapeutic windows. ..
- Hajihosseini M, Heath J. Expression patterns of fibroblast growth factors-18 and -20 in mouse embryos is suggestive of novel roles in calvarial and limb development. Mech Dev. 2002;113:79-83 pubmed
- KUCHIBHOTLA K, Wegmann S, Kopeikina K, Hawkes J, Rudinskiy N, Andermann M, et al. Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo. Proc Natl Acad Sci U S A. 2014;111:510-4 pubmed publisher..These results suggest a reevaluation of the common assumption that insoluble tau aggregates are sufficient to disrupt neuronal function. ..
- Koss D, Robinson L, Drever B, PluciÅ„ska K, Stoppelkamp S, Veselcic P, et al. Mutant Tau knock-in mice display frontotemporal dementia relevant behaviour and histopathology. Neurobiol Dis. 2016;91:105-23 pubmed publisher..Together, our data demonstrate that the transgenic PLB2Tau mouse model presents with a striking behavioural and physiological face validity relevant for FTD, driven by the low level expression of mutant FTD hTau. ..
- Bachler M, Neubüser A. Expression of members of the Fgf family and their receptors during midfacial development. Mech Dev. 2001;100:313-6 pubmed..5. In contrast to the restricted expression patterns of the ligands, FgfR1 and FgfR2 were broadly expressed in facial mesenchyme and ectoderm, respectively, indicating a wide competence of midfacial tissue to respond to FGF signaling. ..
- Bennett R, DeVos S, Dujardin S, Corjuc B, Gor R, Gonzalez J, et al. Enhanced Tau Aggregation in the Presence of Amyloid ?. Am J Pathol. 2017;187:1601-1612 pubmed publisher..Overall, these data provide evidence that amyloid ? acts to enhance tau pathology by increasing the formation of tau species capable of seeding new aggregates. ..
- Fu H, Rodriguez G, Herman M, Emrani S, Nahmani E, Barrett G, et al. Tau Pathology Induces Excitatory Neuron Loss, Grid Cell Dysfunction, and Spatial Memory Deficits Reminiscent of Early Alzheimer's Disease. Neuron. 2017;93:533-541.e5 pubmed publisher..Therefore, tau pathology initiated in the entorhinal cortex could lead to deficits in grid cell firing and underlie the deterioration of spatial cognition seen in human AD. ..
- Delic V, Brownlow M, Joly Amado A, Zivkovic S, Noble K, Phan T, et al. Calorie restriction does not restore brain mitochondrial function in P301L tau mice, but it does decrease mitochondrial F0F1-ATPase activity. Mol Cell Neurosci. 2015;67:46-54 pubmed publisher..This decrease in F0F1-ATPase activity was not due to lowered levels of the alpha or beta subunits of F0F1-ATPase. The possible mechanisms through which CR reduces the F0F1-ATPase activity in brain mitochondria are discussed. ..
- Bailey R, Howard J, Knight J, Sahara N, Dickson D, Lewis J. Effects of the C57BL/6 strain background on tauopathy progression in the rTg4510 mouse model. Mol Neurodegener. 2014;9:8 pubmed publisher..These studies support the use of the rTg4510 mouse model on a partial C57BL/6 strain background without losing fidelity of the phenotype and suggest that the C57BL/6 background does not inherently protect against tauopathy. ..
- Menkes Caspi N, Yamin H, Kellner V, Spires Jones T, Cohen D, Stern E. Pathological tau disrupts ongoing network activity. Neuron. 2015;85:959-66 pubmed publisher..By changing the activity patterns of a subpopulation of affected neurons, pathological tau reduces the activity of the neocortical network. ..
- Bosch M, Nerbonne J, Ornitz D. Dual transgene expression in murine cerebellar Purkinje neurons by viral transduction in vivo. PLoS ONE. 2014;9:e104062 pubmed publisher..AAV1 with a CAG promoter is highly efficient and selective at transducing adult cerebellar Purkinje neurons and two AAV-CAG viruses can be used to efficiently express two proteins in the same neuron in vivo. ..
- Yamamoto S, Mikami T, Konishi M, Itoh N. Stage-specific expression of a novel isoform of mouse FGF-14 (FHF-4) in spermatocytes. Biochim Biophys Acta. 2000;1490:121-4 pubmed
- Hunt J, Nash K, Placides D, Moran P, Selenica M, Abuqalbeen F, et al. Sustained Arginase 1 Expression Modulates Pathological Tau Deposits in a Mouse Model of Tauopathy. J Neurosci. 2015;35:14842-60 pubmed publisher..These data suggest that Arg1 and the polyamine pathway may offer novel therapeutic targets for tauopathies. ..
- d Abramo C, Acker C, Schachter J, Terracina G, Wang X, Forest S, et al. Detecting tau in serum of transgenic animal models after tau immunotherapy treatment. Neurobiol Aging. 2016;37:58-65 pubmed publisher..Levels of tau in human serum are less than the sensitivity of current assays, although artifactual signals are common. The method may be useful in similarly treated humans, a situation in which false positive signals are likely. ..
- Joly Amado A, Serraneau K, Brownlow M, Marin de Evsikova C, Speakman J, Gordon M, et al. Metabolic changes over the course of aging in a mouse model of tau deposition. Neurobiol Aging. 2016;44:62-73 pubmed publisher..These diverse changes in metabolism in a mouse model of tau deposition are discussed in the context of known changes in energy metabolism in Alzheimer's disease. ..
- Tracy T, Sohn P, Minami S, Wang C, Min S, Li Y, et al. Acetylated Tau Obstructs KIBRA-Mediated Signaling in Synaptic Plasticity and Promotes Tauopathy-Related Memory Loss. Neuron. 2016;90:245-60 pubmed publisher..In AD patients with dementia, we found enhanced tau acetylation is linked to loss of KIBRA. These findings suggest a novel mechanism by which pathogenic tau causes synaptic dysfunction and cognitive decline in AD pathogenesis...
- Hägglund A, Dahl L, Carlsson L. Lhx2 is required for patterning and expansion of a distinct progenitor cell population committed to eye development. PLoS ONE. 2011;6:e23387 pubmed publisher..Thus, we have defined a distinct progenitor cell population in the forebrain committed to eye development and identified genes linked to Lhx2's function in the expansion and patterning of these progenitor cells. ..
- Xia Y, Herlitz L, Gindea S, Wen J, Pawar R, Misharin A, et al. Deficiency of fibroblast growth factor-inducible 14 (Fn14) preserves the filtration barrier and ameliorates lupus nephritis. J Am Soc Nephrol. 2015;26:1053-70 pubmed publisher..Thus, blocking the TWEAK/Fn14 axis may be a novel therapeutic intervention in immune-mediated proliferative GN. ..
- Baker J, Shelton L, Zheng D, Favretto F, Nordhues B, Darling A, et al. Human cyclophilin 40 unravels neurotoxic amyloids. PLoS Biol. 2017;15:e2001336 pubmed publisher..This study identifies a novel human protein disaggregase and, for the first time, demonstrates its capacity to dissolve intracellular amyloids. ..
- Hsu W, Scala F, Nenov M, Wildburger N, Elferink H, Singh A, et al. CK2 activity is required for the interaction of FGF14 with voltage-gated sodium channels and neuronal excitability. FASEB J. 2016;30:2171-86 pubmed publisherRecent data shows that fibroblast growth factor 14 (FGF14) binds to and controls the function of the voltage-gated sodium (Nav) channel with phenotypic outcomes on neuronal excitability...
- Booth C, Witton J, Nowacki J, Tsaneva Atanasova K, Jones M, Randall A, et al. Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy. J Neurosci. 2016;36:350-63 pubmed publisher..These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention. ..
- Booth C, Ridler T, Murray T, Ward M, de Groot E, Goodfellow M, et al. Electrical and Network Neuronal Properties Are Preferentially Disrupted in Dorsal, But Not Ventral, Medial Entorhinal Cortex in a Mouse Model of Tauopathy. J Neurosci. 2016;36:312-24 pubmed publisher..Our data suggest that neural signals arising in the mEC will have a reduced spatial content in dementia. ..
- Sankaranarayanan S, Barten D, Vana L, Devidze N, Yang L, Cadelina G, et al. Passive immunization with phospho-tau antibodies reduces tau pathology and functional deficits in two distinct mouse tauopathy models. PLoS ONE. 2015;10:e0125614 pubmed publisher..These studies provide evidence supporting the use of tau immunotherapy as a potential treatment option for AD and other tauopathies. ..
- Ali Y, Allen H, Yu L, Li Kroeger D, Bakhshizadehmahmoudi D, Hatcher A, et al. NMNAT2:HSP90 Complex Mediates Proteostasis in Proteinopathies. PLoS Biol. 2016;14:e1002472 pubmed publisher..Taken together, our data indicate that NMNAT2 exerts its chaperone or enzymatic function in a context-dependent manner to maintain neuronal health. ..
- Schirer Y, Malishkevich A, Ophir Y, Lewis J, Giladi E, Gozes I. Novel marker for the onset of frontotemporal dementia: early increase in activity-dependent neuroprotective protein (ADNP) in the face of Tau mutation. PLoS ONE. 2014;9:e87383 pubmed publisher..Future research into ADNP/tau relations is warranted. ..