Genomes and Genes
Gene Symbol: Nefh
Description: neurofilament, heavy polypeptide
Alias: NF-H, NF200, Nfh, mKIAA0845, neurofilament heavy polypeptide, 200 kDa neurofilament protein, neurofilament 200kDa, neurofilament triplet H protein
- Lees J, Shneidman P, Skuntz S, Carden M, Lazzarini R. The structure and organization of the human heavy neurofilament subunit (NF-H) and the gene encoding it. EMBO J. 1988;7:1947-55 pubmed..The human NF-H gene has three introns, two of which interrupt the protein-coding sequence at identical points to introns in the genes for the two smaller NF proteins, NF-M and NF-L.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Gould T, Yonemura S, Oppenheim R, Ohmori S, Enomoto H. The neurotrophic effects of glial cell line-derived neurotrophic factor on spinal motoneurons are restricted to fusimotor subtypes. J Neurosci. 2008;28:2131-46 pubmed publisher..Therefore, although GDNF influences several aspects of MN development, the survival-promoting effects of GDNF during programmed cell death are mostly confined to spindle-innervating MNs. ..
- Yuan A, Rao M, Sasaki T, Chen Y, Kumar A, Veeranna -, et al. Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS. J Neurosci. 2006;26:10006-19 pubmed
- Rao M, Garcia M, Miyazaki Y, Gotow T, Yuan A, Mattina S, et al. Gene replacement in mice reveals that the heavily phosphorylated tail of neurofilament heavy subunit does not affect axonal caliber or the transit of cargoes in slow axonal transport. J Cell Biol. 2002;158:681-93 pubmed..Most surprisingly, at least in optic nerve axons, loss of the NF-H tail does not affect the rate of transport of neurofilament subunits. ..
- Elder G, Friedrich V, Kang C, Bosco P, Gourov A, Tu P, et al. Requirement of heavy neurofilament subunit in the development of axons with large calibers. J Cell Biol. 1998;143:195-205 pubmed..These results demonstrate directly that unlike losing the NF-L or NF-M subunits, loss of NF-H has only a slight effect on NF number in axons. Yet NF-H plays a major role in the development of large diameter axons. ..
- Marszalek J, Williamson T, Lee M, Xu Z, Hoffman P, Becher M, et al. Neurofilament subunit NF-H modulates axonal diameter by selectively slowing neurofilament transport. J Cell Biol. 1996;135:711-24 pubmed
- Eyer J, Peterson A. Neurofilament-deficient axons and perikaryal aggregates in viable transgenic mice expressing a neurofilament-beta-galactosidase fusion protein. Neuron. 1994;12:389-405 pubmed..mice expressing a fusion protein in which the carboxyl terminus of the high molecular weight neurofilament protein (NFH) was replaced by beta-galactosidase. The transgene, regulated by NFH sequences, was expressed in projection neurons...
- Maricich S, Wellnitz S, Nelson A, Lesniak D, Gerling G, Lumpkin E, et al. Merkel cells are essential for light-touch responses. Science. 2009;324:1580-2 pubmed publisher..Merkel cells are, therefore, required for the proper encoding of Merkel receptor responses, suggesting that these cells form an indispensible part of the somatosensory system. ..
- Bourane S, Garces A, Venteo S, Pattyn A, Hubert T, Fichard A, et al. Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signaling. Neuron. 2009;64:857-70 pubmed publisher..Our results provide evidence that genetic interactions involving Ret and MafA progressively promote the differentiation and diversification of LTMs. ..
- Appler J, Lu C, Druckenbrod N, Yu W, Koundakjian E, Goodrich L. Gata3 is a critical regulator of cochlear wiring. J Neurosci. 2013;33:3679-91 pubmed publisher..As the first auditory-specific regulator of SGN development, Gata3 provides a useful molecular entry point for efforts to engineer SGNs for the restoration of hearing. ..
- Cote F, Collard J, Julien J. Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis. Cell. 1993;73:35-46 pubmed
- Rao M, Houseweart M, Williamson T, Crawford T, Folmer J, Cleveland D. Neurofilament-dependent radial growth of motor axons and axonal organization of neurofilaments does not require the neurofilament heavy subunit (NF-H) or its phosphorylation. J Cell Biol. 1998;143:171-81 pubmed
- Dowling J, Yang Y, Wollmann R, Reichardt L, Fuchs E. Developmental expression of BPAG1-n: insights into the spastic ataxia and gross neurologic degeneration in dystonia musculorum mice. Dev Biol. 1997;187:131-42 pubmed..Collectively, our findings suggest a mechanism for the BPAG1 null phenotype and indicate that different neurons respond differently to the absence of BPAG1-n, a cytoskeletal linker protein. ..
- Zhu Q, Lindenbaum M, Levavasseur F, Jacomy H, Julien J. Disruption of the NF-H gene increases axonal microtubule content and velocity of neurofilament transport: relief of axonopathy resulting from the toxin beta,beta'-iminodipropionitrile. J Cell Biol. 1998;143:183-93 pubmed..These results indicate that the NF-H subunit is a key mediator of IDPN-induced axonopathy. ..
- Collard J, Cote F, Julien J. Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature. 1995;375:61-4 pubmed
- Figlewicz D, Krizus A, Martinoli M, Meininger V, Dib M, Rouleau G, et al. Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum Mol Genet. 1994;3:1757-61 pubmed..The C-terminal region of the human neurofilament heavy subunit (NEFH) contains a unique functional domain consisting of 43 repeat motifs of the amino acids Lys-Ser-Pro (KSP)...
- Parhad I, Scott J, Cellars L, Bains J, Krekoski C, Clark A. Axonal atrophy in aging is associated with a decline in neurofilament gene expression. J Neurosci Res. 1995;41:355-66 pubmed..Although the mechanisms leading to the decrease in Nf gene expression with aging are not known, a decrease in the availability of growth factors, or the neuron's ability to respond to them, may play a role in this process. ..
- Yeung R, Buetow K, Testa J, Knudson A. Susceptibility to renal carcinoma in the Eker rat involves a tumor suppressor gene on chromosome 10. Proc Natl Acad Sci U S A. 1993;90:8038-42 pubmed..Our result suggested that the human homolog of the RC gene may reside on human chromosome 16, not known to be altered commonly in human RC. ..
- Woo S, Baba Y, Franco A, Lumpkin E, Owens D. Excitatory glutamate is essential for development and maintenance of the piloneural mechanoreceptor. Development. 2012;139:740-8 pubmed publisher..The molecular basis for piloneural development, maintenance and function is poorly understood. Here, we show that Nefh-expressing glutamatergic neurons represent a major population of longitudinal and circumferential sensory afferents ..
- Mallucci G, Ratte S, Asante E, Linehan J, Gowland I, Jefferys J, et al. Post-natal knockout of prion protein alters hippocampal CA1 properties, but does not result in neurodegeneration. EMBO J. 2002;21:202-10 pubmed..Furthermore, they show that acute depletion of PrP does not affect neuronal survival in this model, ruling out loss of PrP function as a pathogenic mechanism in prion disease and validating therapeutic approaches targeting PrP. ..
- Wang Y, Thekdi N, Smallwood P, Macke J, Nathans J. Frizzled-3 is required for the development of major fiber tracts in the rostral CNS. J Neurosci. 2002;22:8563-73 pubmed..These data provide the first link between Frizzled signaling and axonal development. ..
- Yan X, Sabrautzki S, Horsch M, Fuchs H, Gailus Durner V, Beckers J, et al. Peroxidasin is essential for eye development in the mouse. Hum Mol Genet. 2014;23:5597-614 pubmed publisher..Our studies provide pathogenic mechanisms of PXDN mutation-induced congenital eye diseases. ..
- Dahlstrand J, Lardelli M, Lendahl U. Nestin mRNA expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system. Brain Res Dev Brain Res. 1995;84:109-29 pubmed
- Save M, Shetty V, Shetty K. Hypophosphorylation of NF-H and NF-M subunits of neurofilaments and the associated decrease in KSPXK kinase activity in the sciatic nerves of swiss white mice inoculated in the foot pad with mycobacterium leprae. Lepr Rev. 2009;80:388-401 pubmed..leprae. The hypophosphorylation of NF observed in this study corroborates with the earlier observations in human leprous nerves. ..
- Elg S, Marmigere F, Mattsson J, Ernfors P. Cellular subtype distribution and developmental regulation of TRPC channel members in the mouse dorsal root ganglion. J Comp Neurol. 2007;503:35-46 pubmed..Our results suggest important roles of the TRPC family of channels in sensory physiology of both nociceptive as well as nonnociceptive classes of neurons. ..
- Páez P, Batiz L, Roales Buján R, Rodríguez Pérez L, Rodriguez S, Jiménez A, et al. Patterned neuropathologic events occurring in hyh congenital hydrocephalic mutant mice. J Neuropathol Exp Neurol. 2007;66:1082-92 pubmed..All evidence collected on hydrocephalic hyh mutant mice indicates that a primary alteration in the neuroepithelium/ependyma cell lineage triggers both hydrocephalus and abnormalities in telencephalic development. ..
- Lim E, Kim I, Oh S, Chun M. Identification and characterization of SMI32-immunoreactive amacrine cells in the mouse retina. Neurosci Lett. 2007;424:199-202 pubmed
- Ball S, Moseley H, Peters J. Mor2, supernatant malate dehydrogenase, is linked to wa2 and Hba on mouse chromosome 11 in a region of homology with human chromosome 2p. Genomics. 1994;24:399-400 pubmed
- Bekku Y, Su W, Hirakawa S, Fassler R, Ohtsuka A, Kang J, et al. Molecular cloning of Bral2, a novel brain-specific link protein, and immunohistochemical colocalization with brevican in perineuronal nets. Mol Cell Neurosci. 2003;24:148-59 pubmed..Our results suggest that Bral2 is involved in the formation of extracellular matrix contributing to perineuronal nets and facilitate the understanding of a functional role of these extracellular matrices. ..
- Goryunov D, He C, Lin C, Leung C, Liem R. Nervous-tissue-specific elimination of microtubule-actin crosslinking factor 1a results in multiple developmental defects in the mouse brain. Mol Cell Neurosci. 2010;44:1-14 pubmed publisher..Embryonic neurons showed a defect in traversing the cortical plate. Our data suggest a critical role for MACF1 in neuronal migration that is dependent on its ability to interact with both microfilaments and microtubules. ..
- Nguyen M, Larivière R, Julien J. Reduction of axonal caliber does not alleviate motor neuron disease caused by mutant superoxide dismutase 1. Proc Natl Acad Sci U S A. 2000;97:12306-11 pubmed..These results do not support the current view that high NF content and large caliber of axons may account for the selective vulnerability of motor neurons in ALS caused by mutant SOD1. ..
- Lalonde R, Dubois M, Strazielle C, Eyer J. Motor coordination and spatial orientation are affected by neurofilament maldistribution: correlations with regional brain activity of cytochrome oxidase. Exp Brain Res. 1999;126:223-34 pubmedb>NFH-LacZ transgenic mice are characterized by an early accumulation of the neurofilament cytoskeleton in the cell bodies of neurons with age-associated abnormalities of motor neurons and cerebellar Purkinje cells...
- Guidi L, Mattley J, Martinez Garay I, Monaco A, Linden J, Velayos Baeza A, et al. Knockout Mice for Dyslexia Susceptibility Gene Homologs KIAA0319 and KIAA0319L have Unaffected Neuronal Migration but Display Abnormal Auditory Processing. Cereb Cortex. 2017;27:5831-5845 pubmed publisher..Overall, these results stand against the proposed role of KIAA0319 and AU040320 in neuronal migration and outline their relationship with deficits in the auditory system. ..
- Jung C, Lee S, Ortiz D, Zhu Q, Julien J, Shea T. The high and middle molecular weight neurofilament subunits regulate the association of neurofilaments with kinesin: inhibition by phosphorylation of the high molecular weight subunit. Brain Res Mol Brain Res. 2005;141:151-5 pubmed..They further indicate that phosphorylation of NF-H dissociates NFs from kinesin and provides a mechanism by which NF-H phosphorylation can contribute to the slowing of NF axonal transport. ..
- Rasin M, Gazula V, Breunig J, Kwan K, Johnson M, Liu Chen S, et al. Numb and Numbl are required for maintenance of cadherin-based adhesion and polarity of neural progenitors. Nat Neurosci. 2007;10:819-27 pubmed..Thus, by regulating RGC adhesion and polarity, Numb and Numbl are required for the tissue architecture of neurogenic niches and the cerebral cortex. ..
- Irla M, Saade M, Fernandez C, Chasson L, Victorero G, Dahmane N, et al. Neuronal distribution of spatial in the developing cerebellum and hippocampus and its somatodendritic association with the kinesin motor KIF17. Exp Cell Res. 2007;313:4107-19 pubmed..These findings suggest that Spatial may play a role in neuronal morphogenesis and synaptic plasticity through its interaction with the kinesin motor KIF17 in dendrites. ..
- Coate T, Raft S, Zhao X, Ryan A, Crenshaw E, Kelley M. Otic mesenchyme cells regulate spiral ganglion axon fasciculation through a Pou3f4/EphA4 signaling pathway. Neuron. 2012;73:49-63 pubmed publisher..These results indicate a model whereby Pou3f4 in the otic mesenchyme establishes an Eph/ephrin-mediated fasciculation signal that promotes inner radial bundle formation. ..
- Brandt Bohne U, Keene D, White F, Koch M. MEGF9: a novel transmembrane protein with a strong and developmentally regulated expression in the nervous system. Biochem J. 2007;401:447-57 pubmed..MEGF9 represents a novel putative receptor, expressed in neuronal and non-neuronal tissues, that is regulated during development and could function as a guidance or signalling molecule. ..
- Ohno M, Hiraoka Y, Matsuoka T, Tomimoto H, Takao K, Miyakawa T, et al. Nardilysin regulates axonal maturation and myelination in the central and peripheral nervous system. Nat Neurosci. 2009;12:1506-13 pubmed publisher..On the basis of these data, we propose that NRDc regulates axonal maturation and myelination in the CNS and PNS, in part, through the modulation of NRG1 shedding. ..
- Sessa A, Mao C, Hadjantonakis A, Klein W, Broccoli V. Tbr2 directs conversion of radial glia into basal precursors and guides neuronal amplification by indirect neurogenesis in the developing neocortex. Neuron. 2008;60:56-69 pubmed publisher..Together, these findings identify Tbr2 as a critical factor for the specification of IPCs during corticogenesis. ..
- Excoffon K, Avenarius M, Hansen M, Kimberling W, Najmabadi H, Smith R, et al. The Coxsackievirus and Adenovirus Receptor: a new adhesion protein in cochlear development. Hear Res. 2006;215:1-9 pubmed
- Sun W, Gould T, Newbern J, Milligan C, Choi S, Kim H, et al. Phosphorylation of c-Jun in avian and mammalian motoneurons in vivo during programmed cell death: an early reversible event in the apoptotic cascade. J Neurosci. 2005;25:5595-603 pubmed..Together, c-Jun phosphorylation appears to be required for the initiation of an early and reversible event in the intracellular PCD cascade in vivo after loss of survival-promoting signals such as neurotrophic factors. ..
- Plump A, Erskine L, Sabatier C, Brose K, Epstein C, Goodman C, et al. Slit1 and Slit2 cooperate to prevent premature midline crossing of retinal axons in the mouse visual system. Neuron. 2002;33:219-32 pubmed..Our results indicate that Slit proteins repel retinal axons in vivo and cooperate to establish a corridor through which the axons are channeled, thereby helping define the site in the ventral diencephalon where the optic chiasm forms. ..
- Graus Porta D, Blaess S, Senften M, Littlewood Evans A, Damsky C, Huang Z, et al. Beta1-class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortex. Neuron. 2001;31:367-79 pubmed..The phenotype of the beta1-deficient mice resembles pathological changes observed in human cortical dysplasias, suggesting that defective integrin-mediated signal transduction contributes to the development of some of these diseases. ..
- Perrone Capano C, Pernas Alonso R, di Porzio U. Neurofilament homeostasis and motoneurone degeneration. Bioessays. 2001;23:24-33 pubmed..BioEssays 23:24-33, 2001. ..
- Ernfors P, Lee K, Jaenisch R. Mice lacking brain-derived neurotrophic factor develop with sensory deficits. Nature. 1994;368:147-50 pubmed..Survival of sympathetic, midbrain dopaminergic and motor neurons is not affected. These results indicate that BDNF is required for the survival and target innervation of particular neuronal populations. ..
- Tu P, Robinson K, de Snoo F, Eyer J, Peterson A, Lee V, et al. Selective degeneration fo Purkinje cells with Lewy body-like inclusions in aged NFHLACZ transgenic mice. J Neurosci. 1997;17:1064-74 pubmed..mice expressing a fusion protein composed of a truncated high-molecular-weight mouse neurofilament (NF) protein (NFH) fused to beta-galactosidase (LacZ) develop inclusions in neurons throughout the CNS...
- van de Pavert S, Olivier B, Goverse G, Vondenhoff M, Greuter M, Beke P, et al. Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation. Nat Immunol. 2009;10:1193-9 pubmed publisher..Therefore, our data show that the initiation of lymph node development is controlled by RA-mediated expression of CXCL13 and suggest that RA may be provided by adjacent neurons. ..
- Akil O, Weber C, Park S, Ninkina N, Buchman V, Lustig L. Localization of synucleins in the mammalian cochlea. J Assoc Res Otolaryngol. 2008;9:452-63 pubmed publisher..Whether overlapping roles of the other synucleins help compensate for the loss of gamma-synuclein remains to be determined. ..
- Gan L, Xiang M, Zhou L, Wagner D, Klein W, Nathans J. POU domain factor Brn-3b is required for the development of a large set of retinal ganglion cells. Proc Natl Acad Sci U S A. 1996;93:3920-5 pubmed..In Brn-3b (-/-) mice other neurons within the retina and brain are minimally or not at all affected. These experiments indicate that Brn-3b plays an essential role in the development of specific ganglion cell types. ..
- Guha U, Gomes W, Samanta J, Gupta M, Rice F, Kessler J. Target-derived BMP signaling limits sensory neuron number and the extent of peripheral innervation in vivo. Development. 2004;131:1175-86 pubmed
- Stark D, Coffey N, Pancoast H, Arnold L, Walker J, VallÃ©e J, et al. Ephrin-A3 promotes and maintains slow muscle fiber identity during postnatal development and reinnervation. J Cell Biol. 2015;211:1077-91 pubmed publisher..We therefore conclude that Eph/ephrin interactions guide the fiber type specificity of neuromuscular interactions during development and adult life. ..