Genomes and Genes
Gene Symbol: Grhl3
Description: grainyhead like transcription factor 3
Alias: AI561912, Get1, Som, Tfcp2l4, grainyhead-like protein 3 homolog, grainy head-like 3, grainyhead-like 3, sister-of-mammalian grainyhead, transcription factor CP2-like 4, transcription factor hSOM1
- van Straaten H, Blom H, Peeters M, Rousseau A, Cole K, Seller M. Dietary methionine does not reduce penetrance in curly tail mice but causes a phenotype-specific decrease in embryonic growth. J Nutr. 1995;125:2733-40 pubmed..We conclude that L-methionine does not reduce penetrance in the curly tail mouse and that this strain reflects no derangement in L-methionine handling. ..
- Rifat Y, Parekh V, Wilanowski T, Hislop N, Auden A, Ting S, et al. Regional neural tube closure defined by the Grainy head-like transcription factors. Dev Biol. 2010;345:237-45 pubmed publisher..Loss of Grhl3 alone defines a distinct lower spinal closure defect, also with defective DLHP formation...
- Brook F, Shum A, van Straaten H, Copp A. Curvature of the caudal region is responsible for failure of neural tube closure in the curly tail (ct) mouse embryo. Development. 1991;113:671-8 pubmed..Increased ventral curvature may arise as a result of a cell proliferation imbalance, which we demonstrated previously in affected ct/ct embryos. ..
- Gustavsson P, Greene N, Lad D, Pauws E, de Castro S, Stanier P, et al. Increased expression of Grainyhead-like-3 rescues spina bifida in a folate-resistant mouse model. Hum Mol Genet. 2007;16:2640-6 pubmed..Grainyhead-like-3 (Grhl3), which encodes a transcription factor, was recently identified as a candidate gene for curly tail based on ..
- Greene N, Copp A. Inositol prevents folate-resistant neural tube defects in the mouse. Nat Med. 1997;3:60-6 pubmed..Our findings reveal a molecular pathway of NTD prevention and suggest the possible efficacy of combined treatment with folate and inositol in overcoming the majority of human NTDs. ..
- Seller M, Embury S, Polani P, Adinolfi M. Neural tube defects in curly-tail mice. II. Effect of maternal administration of vitamin A. Proc R Soc Lond B Biol Sci. 1979;206:95-107 pubmed..t.d. decreased rather than increased. Furthermore, the number of mice affected by n.t.d. was markedly lower even than that found spontaneously in untreated curly-tail mice. ..
- Werth M, Walentin K, Aue A, Schönheit J, Wuebken A, Pode Shakked N, et al. The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex. Development. 2010;137:3835-45 pubmed publisher..Together, our data provide evidence that Grhl2 acts as a target gene-associated transcriptional activator of apical junctional complex components and, thereby, crucially participates in epithelial differentiation. ..
- Burren K, Scott J, Copp A, Greene N. The genetic background of the curly tail strain confers susceptibility to folate-deficiency-induced exencephaly. Birth Defects Res A Clin Mol Teratol. 2010;88:76-83 pubmed publisher..caused a similar-sized, statistically significant increase in the frequency of cranial NTDs among both curly tail (Grhl3 mutant) embryos and background-matched embryos that are wild type for Grhl3...
- Cogram P, Hynes A, Dunlevy L, Greene N, Copp A. Specific isoforms of protein kinase C are essential for prevention of folate-resistant neural tube defects by inositol. Hum Mol Genet. 2004;13:7-14 pubmed..Hindgut cell proliferation was stimulated specifically by inositol, an effect that required activation of PKCbetaI. Our findings reveal an essential role of specific PKC isoforms in mediating the prevention of mouse NTDs by inositol. ..
- Tran P, Hiou Tim F, Frosst P, Lussier Cacan S, Bagley P, Selhub J, et al. The curly-tail (ct) mouse, an animal model of neural tube defects, displays altered homocysteine metabolism without folate responsiveness or a defect in Mthfr. Mol Genet Metab. 2002;76:297-304 pubmed
- Cockroft D, Brook F, Copp A. Inositol deficiency increases the susceptibility to neural tube defects of genetically predisposed (curly tail) mouse embryos in vitro. Teratology. 1992;45:223-32 pubmed..PO embryos showed a lower proportion (5/19) of cranial NTD in the inositol deficient medium than the other two strains, and this was further reduced by even the lowest inositol dose. ..
- Letts V, Schork N, Copp A, Bernfield M, Frankel W. A curly-tail modifier locus, mct1, on mouse chromosome 17. Genomics. 1995;29:719-24 pubmed..spretus cross and was the preferred model overall. No evidence was found for epistatic interaction between ct and mct1. ..
- Chen W, Morriss Kay G, Copp A. Genesis and prevention of spinal neural tube defects in the curly tail mutant mouse: involvement of retinoic acid and its nuclear receptors RAR-beta and RAR-gamma. Development. 1995;121:681-91 pubmed..These results suggest that the spinal neural tube defects which characterise the curly tail phenotype may be due to interaction between the ct gene product and one or more aspects of the retinoic acid signalling pathway. ..
- Yu Z, Bhandari A, Mannik J, Pham T, Xu X, Andersen B. Grainyhead-like factor Get1/Grhl3 regulates formation of the epidermal leading edge during eyelid closure. Dev Biol. 2008;319:56-67 pubmed publisher..One such factor, the mammalian Grainyhead-like epithelial transactivator (Get1/Grhl3), is important for epidermal barrier formation...
- Neumann P, Frankel W, Letts V, Coffin J, Copp A, Bernfield M. Multifactorial inheritance of neural tube defects: localization of the major gene and recognition of modifiers in ct mutant mice. Nat Genet. 1994;6:357-62 pubmed..This study provides definitive evidence for multifactorial inheritance in a mouse model of human NTD. ..
- Camerer E, Barker A, Duong D, Ganesan R, Kataoka H, Cornelissen I, et al. Local protease signaling contributes to neural tube closure in the mouse embryo. Dev Cell. 2010;18:25-38 pubmed publisher..Together, our results suggest a role for protease-activated receptor signaling in neural tube closure and identify a local protease network that may trigger Par2 signaling and monitor and regulate epithelial integrity in this context. ..
- Caddy J, Wilanowski T, Darido C, Dworkin S, Ting S, Zhao Q, et al. Epidermal wound repair is regulated by the planar cell polarity signaling pathway. Dev Cell. 2010;19:138-47 pubmed publisher..Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing, neural tube defects, and disordered cochlear polarity...
- Ting S, Caddy J, Wilanowski T, Auden A, Cunningham J, Elias P, et al. The epidermis of grhl3-null mice displays altered lipid processing and cellular hyperproliferation. Organogenesis. 2005;2:33-5 pubmed..This gene, Grainy head-like 3 (Grhl3) is a member of a large family of transcription factors that are homologs of the Drosophila developmental gene ..
- Hemre K, Keller Peck C, Campbell R, Peterson A, Mullen R, Goldowitz D. Annexin IV is a marker of roof and floor plate development in the murine CNS. J Comp Neurol. 1996;368:527-37 pubmed
- Adinolfi M, Beck S, Embury S, Polani P, Seller M. Levels of alpha-fetoprotein in amniotic fluids of mice (curly-tail) with neural tube defects. J Med Genet. 1976;13:511-3 pubmed..This suggests that these mice are a valid model for studies of the aetiology and genesis of neural tube defects in man. ..
- Harris M, Juriloff D. Mini-review: toward understanding mechanisms of genetic neural tube defects in mice. Teratology. 1999;60:292-305 pubmed
- Brouns M, Peeters M, Geurts J, Merckx D, Engelen J, Hekking J, et al. Toward positional cloning of the curly tail gene. Birth Defects Res A Clin Mol Teratol. 2005;73:154-61 pubmed..Supplementary material for this article can be found on the Birth Defects Research (Part A) website (http://www.mrw.interscience.wiley.com/suppmat/1542-0752/suppmat/2005/73/tables_S3-S6.doc). ..
- Guardiola Serrano F, Haendeler J, Lukosz M, Sturm K, Melchner H, Altschmied J. Gene trapping identifies a putative tumor suppressor and a new inducer of cell migration. Biochem Biophys Res Commun. 2008;376:748-52 pubmed publisher..these were the genes coding for the zinc finger protein ZC3H10 and for the transcription factor grainyhead-like 3 (GRHL3)...
- Gofflot F, Hall M, Morriss Kay G. Genetic patterning of the posterior neuropore region of curly tail mouse embryos: deficiency of Wnt5a expression. Int J Dev Biol. 1998;42:637-44 pubmed..A possible relationship between decreased Wnt5a expression and reduced levels of heparan sulphate proteoglycan is discussed. ..
- Gordon W, Zeller M, Klein R, Swindell W, Ho H, Espetia F, et al. A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia. J Clin Invest. 2014;124:5205-18 pubmed publisher..Here, we determined that the prodifferentiation transcription factor grainyhead-like 3 (GRHL3), which is essential during epidermal development, is dispensable for adult skin homeostasis, but required for ..
- Cangkrama M, Darido C, Georgy S, Partridge D, Auden A, Srivastava S, et al. Two Ancient Gene Families Are Critical for Maintenance of the Mammalian Skin Barrier in Postnatal Life. J Invest Dermatol. 2016;136:1438-1448 pubmed publisher..Embryonic deletion of Grhl3 induces loss of Tgm1 expression, which disrupts the cornified envelope, thus preventing permeability barrier ..
- Bhandari A, Gordon W, Dizon D, Hopkin A, Gordon E, Yu Z, et al. The Grainyhead transcription factor Grhl3/Get1 suppresses miR-21 expression and tumorigenesis in skin: modulation of the miR-21 target MSH2 by RNA-binding protein DND1. Oncogene. 2013;32:1497-507 pubmed publisher..by a complex interplay of transcription factors, including the evolutionarily conserved Grainyhead-like 3 (Grhl3/Get1); Grhl3-deleted mice exhibit impaired epidermal differentiation and decreased expression of multiple ..
- Seller M, Perkins K, Adinolfi M. Differential response of heterozygous curly-tail mouse embryos to vitamin A teratogenesis depending on maternal genotype. Teratology. 1983;28:123-9 pubmed..It is concluded that gene-environment interaction has been demonstrated, together with both a maternal effect and a contribution of the fetal genotype in the liability to produce NTD in response to vitamin A. ..
- Seller M, Adinolfi M. The curly-tail mouse: an experimental model for human neural tube defects. Life Sci. 1981;29:1607-15 pubmed
- Yu Z, Mannik J, Soto A, Lin K, Andersen B. The epidermal differentiation-associated Grainyhead gene Get1/Grhl3 also regulates urothelial differentiation. EMBO J. 2009;28:1890-903 pubmed publisher..highly with that of differentiation markers in both the bladder and skin, including the Grainyhead factor Get1/Grhl3, which is already known to be important for epidermal barrier formation...
- Kousa Y, Roushangar R, Patel N, Walter A, Marangoni P, Krumlauf R, et al. IRF6 and SPRY4 Signaling Interact in Periderm Development. J Dent Res. 2017;96:1306-1313 pubmed publisherRare mutations in IRF6 and GRHL3 cause Van der Woude syndrome, an autosomal dominant orofacial clefting disorder. Common variants in IRF6 and GRHL3 also contribute risk for isolated orofacial clefting...
- Embury S, Seller M, Adinolfi M, Polani P. Neural tube defects in curly-tail mice. I. Incidence, expression and similarity to the human condition. Proc R Soc Lond B Biol Sci. 1979;206:85-94 pubmed..The curly-tail mice thus provide a useful model for the investigation of neural tube defects in man. ..
- Boglev Y, Wilanowski T, Caddy J, Parekh V, Auden A, Darido C, et al. The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity. Dev Biol. 2011;349:512-22 pubmed publisherThe Grainy head-like 3 (Grhl3) gene encodes a transcription factor that plays essential roles in epidermal morphogenesis during embryonic development, with deficient mice exhibiting failed skin barrier formation, defective wound repair, ..
- Dworkin S, Auden A, Partridge D, Daglas M, Medcalf R, Mantamadiotis T, et al. Grainyhead-like 3 (Grhl3) deficiency in brain leads to altered locomotor activity and decreased anxiety-like behaviors in aged mice. Dev Neurobiol. 2017;77:775-788 pubmed publisher..Here they show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to ..
- Georgy S, Cangkrama M, Srivastava S, Partridge D, Auden A, Dworkin S, et al. Identification of a Novel Proto-oncogenic Network in Head and Neck Squamous Cell Carcinoma. J Natl Cancer Inst. 2015;107: pubmed publisherThe developmental transcription factor Grainyhead-like 3 (GRHL3) plays a critical tumor suppressor role in the mammalian epidermis through direct regulation of PTEN and the PI3K/AKT/mTOR signaling pathway...
- Estibeiro J, Brook F, Copp A. Interaction between splotch (Sp) and curly tail (ct) mouse mutants in the embryonic development of neural tube defects. Development. 1993;119:113-21 pubmed..The angle of ventral curvature of the posterior neuropore region is enhanced in affected ct/ct embryos whereas it was found to be reduced in Sp/Sp embryos compared with their normal littermates.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Shum A, Copp A. Regional differences in morphogenesis of the neuroepithelium suggest multiple mechanisms of spinal neurulation in the mouse. Anat Embryol (Berl). 1996;194:65-73 pubmed
- Massarwa R, Niswander L. In toto live imaging of mouse morphogenesis and new insights into neural tube closure. Development. 2013;140:226-36 pubmed publisher..We demonstrate the advantages of this imaging system by following the dynamics of neural tube closure during mouse embryogenesis and reveal extensive movements of the cranial neural tissue that are independent of neural fold zipping. ..
- Peyrard Janvid M, Leslie E, Kousa Y, Smith T, Dunnwald M, Magnusson M, et al. Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development. Am J Hum Genet. 2014;94:23-32 pubmed publisher..In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3)...
- Goldie S, Arhatari B, Anderson P, Auden A, Partridge D, Jane S, et al. Mice lacking the conserved transcription factor Grainyhead-like 3 (Grhl3) display increased apposition of the frontal and parietal bones during embryonic development. BMC Dev Biol. 2016;16:37 pubmed..measurement, we show that genetic deletion of the highly-conserved transcription factor Grainyhead-like 3 (Grhl3) in mice (Grhl3 -/- ) leads to decreased skull size, aberrant skull morphology and premature apposition ..
- Kousa Y, Moussa D, Schutte B. IRF6 expression in basal epithelium partially rescues Irf6 knockout mice. Dev Dyn. 2017;246:670-681 pubmed publisher..In this work, we show that altering the expression level of IRF6 dramatically modified this phenotype in utero. Developmental Dynamics 246:670-681, 2017. © 2017 Wiley Periodicals, Inc. ..
- Frateschi S, Camerer E, Crisante G, Rieser S, Membrez M, Charles R, et al. PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin. Nat Commun. 2011;2:161 pubmed..transgenic expression in mouse skin of either CAP1/Prss8 (K14-CAP1/Prss8) or protease-activated receptor-2 (PAR2; Grhl3(PAR2/+)), one candidate downstream target, causes epidermal hyperplasia, ichthyosis and itching...
- Copp A, Seller M, Polani P. Neural tube development in mutant (curly tail) and normal mouse embryos: the timing of posterior neuropore closure in vivo and in vitro. J Embryol Exp Morphol. 1982;69:151-67 pubmed..This paper constitutes the first demonstration of the development of a genetically induced malformation in vitro. ..
- Hall M, Gofflot F, Iseki S, Morriss Kay G. Effects of the curly tail genotype on neuroepithelial integrity and cell proliferation during late stages of primary neurulation. J Anat. 2001;199:645-55 pubmed..Minor histological and proliferation abnormalities are present in all ct/ct embryos, regardless of phenotype. ..
- Nguyen D, Richter D, Michel G, Mitschka S, Kolanus W, Cuevas E, et al. The ubiquitin ligase LIN41/TRIM71 targets p53 to antagonize cell death and differentiation pathways during stem cell differentiation. Cell Death Differ. 2017;24:1063-1078 pubmed publisher..In vivo, the lack of LIN41 is associated with upregulation of Grhl3 and widespread caspase-3 activation, two downstream effectors of p53 with essential roles in neural tube closure...
- Copp A. Genetic models of mammalian neural tube defects. Ciba Found Symp. 1994;181:118-34; discussion 134-43 pubmed..A combination of genetic analysis, gene cloning and experimental embryology is revealing that neural tube defects in mice and, by implication, in humans are a developmentally heterogeneous group of malformations. ..
- Brouns M, de Castro S, Terwindt Rouwenhorst E, Massa V, Hekking J, Hirst C, et al. Over-expression of Grhl2 causes spina bifida in the Axial defects mutant mouse. Hum Mol Genet. 2011;20:1536-46 pubmed publisher..expressed in the surface ectoderm and hindgut endoderm in the spinal region, overlapping with grainyhead-like 3 (Grhl3). Axd mutants display delayed eyelid closure, as reported in Grhl3 null embryos...
- de Castro S, Malhas A, Leung K, Gustavsson P, Vaux D, Copp A, et al. Lamin b1 polymorphism influences morphology of the nuclear envelope, cell cycle progression, and risk of neural tube defects in mice. PLoS Genet. 2012;8:e1003059 pubmed publisher..These observations indicate a mechanistic link between altered lamin B1 function, exacerbation of the Grhl3-mediated cell proliferation defect, and enhanced susceptibility to NTDs...
- de Castro S, Hirst C, Savery D, Rolo A, Lickert H, Andersen B, et al. Neural tube closure depends on expression of Grainyhead-like 3 in multiple tissues. Dev Biol. 2018;435:130-137 pubmed publisher..Among the genes whose loss of function causes NTDs in mice, Grainyhead-like3 (Grhl3) is essential for spinal neural tube closure, with null mutants exhibiting fully penetrant spina bifida...
- Nadeau J. Modifier genes in mice and humans. Nat Rev Genet. 2001;2:165-74 pubmed
- Selcuki M, Manning S, Bernfield M. The curly tail mouse model of human neural tube defects demonstrates normal spinal cord differentiation at the level of the meningomyelocele: implications for fetal surgery. Childs Nerv Syst. 2001;17:19-23 pubmed..Based on this model, fetal surgery to repair human meningomyelocele may preserve neurological function in those cases where there is not an inherent genetic defect of the neural tissue. ..
- Reis J, Correia Pinto J, Monteiro M, Hutchins G. In utero topographic analysis of astrocytes and neuronal cells in the spinal cord of mutant mice with myelomeningocele. J Neurosurg. 2007;106:472-9 pubmed..This study supports the current concept of placode protection through in utero surgery for fetuses with MMC. ..
- Keller Peck C, Mullen R. Altered cell proliferation in the spinal cord of mouse neural tube mutants curly tail and Pax3 splotch-delayed. Brain Res Dev Brain Res. 1997;102:177-88 pubmed..Several possible explanations for this phenomenon are considered, including the hypothesis that the roof plate, or other factors induced by neural tube closure, might have an anti-mitotic activity. ..
- Peeters M, Shum A, Hekking J, Copp A, van Straaten H. Relationship between altered axial curvature and neural tube closure in normal and mutant (curly tail) mouse embryos. Anat Embryol (Berl). 1996;193:123-30 pubmed
- van Straaten H, Hekking J, Copp A, Bernfield M. Deceleration and acceleration in the rate of posterior neuropore closure during neurulation in the curly tail (ct) mouse embryo. Anat Embryol (Berl). 1992;185:169-74 pubmed..Embryos with large PNPs showed a marked deceleration of closure rate during a period of 11 somite stages, followed by a brief but very high acceleration of closure rate.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Salazar V, Ohte S, Capelo L, Gamer L, Rosen V. Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2. Development. 2016;143:4352-4367 pubmed..Our analysis furthermore reveals Grainyhead-like 3 (Grhl3) as a transcription factor in the osteoblast gene regulatory network induced during bone development and bone ..
- Ray H, Niswander L. Grainyhead-like 2 downstream targets act to suppress epithelial-to-mesenchymal transition during neural tube closure. Development. 2016;143:1192-204 pubmed publisher..Thus, GRHL2 promotes the epithelial nature of the NNE during the dynamic events of neural tube formation by both activating key epithelial genes and actively suppressing EMT through novel downstream EMT suppressors. ..
- Peeters M, Schutte B, Lenders M, Hekking J, Drukker J, van Straaten H. Role of differential cell proliferation in the tail bud in aberrant mouse neurulation. Dev Dyn. 1998;211:382-9 pubmed
- Keller Peck C, Mullen R. Patterns of neuronal differentiation in neural tube mutant mice: curly tail and Pax3 splotch-delayed. J Comp Neurol. 1996;368:516-26 pubmed..However, the anomalous morphological and chemical environment may contribute to the neuronal degeneration observed at later stages. ..
- Wang X, Abraham S, McKenzie J, Jeffs N, Swire M, Tripathi V, et al. LRG1 promotes angiogenesis by modulating endothelial TGF-Î² signalling. Nature. 2013;499:306-11 pubmed publisher..LRG1 antibody blockade inhibits this switch and attenuates angiogenesis. These studies reveal a new regulator of angiogenesis that mediates its effect by modulating TGF-Î² signalling. ..
- Auden A, Caddy J, Wilanowski T, Ting S, Cunningham J, Jane S. Spatial and temporal expression of the Grainyhead-like transcription factor family during murine development. Gene Expr Patterns. 2006;6:964-70 pubmed..Using gene targeting in mice, we have shown that Grhl3 is essential for neural tube closure, skin barrier formation and wound healing...
- Pourhoseini S, Seth R, Das S, Dattaroy D, Kadiiska M, Xie G, et al. Upregulation of miR21 and repression of Grhl3 by leptin mediates sinusoidal endothelial injury in experimental nonalcoholic steatohepatitis. PLoS ONE. 2015;10:e0116780 pubmed publisher..The upregulation of miR21 led to a time-dependent repression of its target protein Grhl3 levels as shown by western blot analyses...
- Bell S, Zhang L, Mendell A, Xu Y, Haitchi H, Lessard J, et al. Kruppel-like factor 5 is required for formation and differentiation of the bladder urothelium. Dev Biol. 2011;358:79-90 pubmed publisher..mRNA analysis identified reductions in Ppar?, Grhl3, Elf3, and Ovol1expression in Klf5 deficient fetal bladders supporting their participation in a transcriptional ..
- Beier D, Dushkin H, Telle T. Haplotype analysis of intra-specific backcross curly-tail mice confirms the localization of ct to chromosome 4. Mamm Genome. 1995;6:269-72 pubmed..Finally, we examined Pax7 as a candidate gene for the ct mutation and found no evidence of protein sequence differences in ct compared with wild-type mice. ..
- Kudryavtseva E, Sugihara T, Wang N, Lasso R, Gudnason J, Lipkin S, et al. Identification and characterization of Grainyhead-like epithelial transactivator (GET-1), a novel mammalian Grainyhead-like factor. Dev Dyn. 2003;226:604-17 pubmed..These data suggest that GET-1 is a transcriptional regulator that may perform important functions in epithelial tissues of mammals. ..