Genomes and Genes
Gene Symbol: Lef1
Description: lymphoid enhancer binding factor 1
Alias: 3000002B05, AI451430, Lef-1, lymphoid enhancer-binding factor 1
- Yamaguchi T, Bradley A, McMahon A, Jones S. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development. 1999;126:1211-23 pubmed..The reduced number of proliferating cells in both the progress zone and the primitive streak mesoderm suggests that one function of Wnt5a is to regulate the proliferation of progenitor cells. ..
- Reya T, O RIORDAN M, Okamura R, Devaney E, Willert K, Nusse R, et al. Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism. Immunity. 2000;13:15-24 pubmed..We further show that Lef1-/- pro-B cells display elevated levels of fas and c-myc transcription, providing a potential mechanism for their ..
- Hardcastle Z, Mo R, Hui C, Sharpe P. The Shh signalling pathway in tooth development: defects in Gli2 and Gli3 mutants. Development. 1998;125:2803-11 pubmed..These results show an essential role for Shh signalling in tooth development that involves functional redundancy of downstream Gli genes...
- Merrill B, Gat U, Dasgupta R, Fuchs E. Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. Genes Dev. 2001;15:1688-705 pubmed..In this paper, we show that Tcf3 and Lef1 control these differentiation lineages...
- Matsushima D, Heavner W, Pevny L. Combinatorial regulation of optic cup progenitor cell fate by SOX2 and PAX6. Development. 2011;138:443-54 pubmed publisher..Collectively, these results demonstrate that precise regulation of the ratio of SOX2 to PAX6 is necessary to ensure accurate progenitor cell specification, and place SOX2 as a decisive factor of neural competence in the retina. ..
- van Genderen C, Okamura R, Farinas I, Quo R, Parslow T, Bruhn L, et al. Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev. 1994;8:2691-703 pubmed..Together, the pattern of these defects suggest an essential role for LEF-1 in the formation of several organs and structures that require inductive tissue interactions. ..
- Huber O, Korn R, McLaughlin J, Ohsugi M, Herrmann B, Kemler R. Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. Mech Dev. 1996;59:3-10 pubmed..As shown for beta-catenin, ectopic expression of LEF-1 in Xenopus embryos caused duplication of the body axis, indicating a regulatory role for a LEF-1-like molecule in dorsal mesoderm formation. ..
- Galceran J, Hsu S, Grosschedl R. Rescue of a Wnt mutation by an activated form of LEF-1: regulation of maintenance but not initiation of Brachyury expression. Proc Natl Acad Sci U S A. 2001;98:8668-73 pubmed..Consistent with this view, mice carrying mutations in either the Wnt3a gene or in both transcription factor genes Lef1 and Tcf1 were previously found to show a similar defect in the formation of paraxial mesoderm in the gastrulating ..
- Chassot A, Ranc F, Gregoire E, Roepers Gajadien H, Taketo M, Camerino G, et al. Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet. 2008;17:1264-77 pubmed publisher..Thus, a balance between Sox9 and beta-catenin activation determines the fate of the gonad, with Rspo1 acting as a crucial regulator of canonical beta-catenin signaling required for female development. ..
- Rhee H, Polak L, Fuchs E. Lhx2 maintains stem cell character in hair follicles. Science. 2006;312:1946-9 pubmed..Using gain- and loss-of-function studies, we uncovered a role for Lhx2 in maintaining the growth and undifferentiated properties of hair follicle progenitors. ..
- Zhu X, Zhu H, Zhang L, Huang S, Cao J, Ma G, et al. Wls-mediated Wnts differentially regulate distal limb patterning and tissue morphogenesis. Dev Biol. 2012;365:328-38 pubmed publisher..These findings provide a comprehensive view of the role of Wnts in limb patterning and tissue morphogenesis...
- Vadlamudi U, Espinoza H, Ganga M, Martin D, Liu X, Engelhardt J, et al. PITX2, beta-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter. J Cell Sci. 2005;118:1129-37 pubmed..LEF-1 and beta-catenin interactions with PITX2 provide new mechanisms for the regulation of PITX2 transcriptional activity. ..
- Ghogomu S, van Venrooy S, Ritthaler M, Wedlich D, Gradl D. HIC-5 is a novel repressor of lymphoid enhancer factor/T-cell factor-driven transcription. J Biol Chem. 2006;281:1755-64 pubmed
- Love J, Li X, Case D, Giese K, Grosschedl R, Wright P. Structural basis for DNA bending by the architectural transcription factor LEF-1. Nature. 1995;376:791-5 pubmed..The structure reveals the HMG domain bound in the widened minor groove of a markedly distorted and bent double helix. The basic region binds across the narrowed major groove and contributes to DNA recognition. ..
- Zhou C, Zhao C, Pleasure S. Wnt signaling mutants have decreased dentate granule cell production and radial glial scaffolding abnormalities. J Neurosci. 2004;24:121-6 pubmed..2000). We examined the hippocampal phenotype of single LRP6 mutant mice as well as LRP6/Lef1 double mutant mice...
- Cho K, Kim J, Song S, Farrell E, Eblaghie M, Kim H, et al. Molecular interactions between Tbx3 and Bmp4 and a model for dorsoventral positioning of mammary gland development. Proc Natl Acad Sci U S A. 2006;103:16788-93 pubmed..In addition, when BMP signaling was inhibited by NOGGIN, Lef1 expression was lost...
- Raveh E, Cohen S, Levanon D, Negreanu V, Groner Y, Gat U. Dynamic expression of Runx1 in skin affects hair structure. Mech Dev. 2006;123:842-50 pubmed..The data delineate Runx1 as a novel specific marker of several hair follicle cell types and sheds light on its role in hair morphogenesis and differentiation. ..
- Travis A, Amsterdam A, Belanger C, Grosschedl R. LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function [corrected]. Genes Dev. 1991;5:880-94 pubmed..Moreover, forced expression of recombinant LEF-1 in late stage B cells increases TCR alpha enhancer function. Taken together, these data suggest that LEF-1 is a regulatory participant in lymphocyte gene expression and differentiation. ..
- Zhang Y, Tomann P, Andl T, Gallant N, Huelsken J, Jerchow B, et al. Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction. Dev Cell. 2009;17:49-61 pubmed publisher..These data reveal a complex interplay and interdependence of Wnt/beta-catenin and EDA/EDAR/NF-kappaB signaling pathways in initiation and maintenance of primary hair follicle placodes...
- Wisniewska M, Misztal K, Michowski W, Szczot M, Purta E, Lesniak W, et al. LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain. J Neurosci. 2010;30:4957-69 pubmed publisherbeta-Catenin, together with LEF1/TCF transcription factors, activates genes involved in the proliferation and differentiation of neuronal precursor cells...
- Hiremath M, Dann P, Fischer J, Butterworth D, Boras Granic K, Hens J, et al. Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme. Development. 2012;139:4239-49 pubmed publisher..differentiation of the ventral epidermis into nipple-like skin and is accompanied by ectopic expression of Lef1, ?-catenin and other markers of the mammary mesenchyme...
- Tebar M, Destree O, de Vree W, Ten Have Opbroek A. Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung. Mech Dev. 2001;109:437-40 pubmed..5 onward), and adjacent mesenchyme. Tcf1, Lef1, Tcf3, Tcf4, sFrp1, sFrp2 and sFrp4 were also expressed in the PE, AE, and adjacent mesenchyme in specific spatio-..
- Song L, Li Y, Wang K, Wang Y, Molotkov A, Gao L, et al. Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion. Development. 2009;136:3161-71 pubmed publisher..Thus, the Lrp6-mediated Wnt signaling pathway is required for lip development by orchestrating two distinctively different morphogenetic movements. ..
- Galceran J, Miyashita Lin E, Devaney E, Rubenstein J, Grosschedl R. Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1. Development. 2000;127:469-82 pubmedb>Lef1 and other genes of the LEF1/TCF family of transcription factors are nuclear mediators of Wnt signaling. Here we examine the expression pattern and functional importance of Lef1 in the developing forebrain of the mouse...
- Kratochwil K, Dull M, Farinas I, Galceran J, Grosschedl R. Lef1 expression is activated by BMP-4 and regulates inductive tissue interactions in tooth and hair development. Genes Dev. 1996;10:1382-94 pubmed..organ development, formation of the epithelial primordium of the whisker but not tooth is dependent on mesenchymal Lef1 gene expression...
- Liu F, Chu E, WATT B, Zhang Y, Gallant N, Andl T, et al. Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Dev Biol. 2008;313:210-24 pubmed
- Guo X, Mak K, Taketo M, Yang Y. The Wnt/beta-catenin pathway interacts differentially with PTHrP signaling to control chondrocyte hypertrophy and final maturation. PLoS ONE. 2009;4:e6067 pubmed publisher..Furthermore, Wnt/beta-catenin signaling also controls final maturation of hypertrophic chondrocytes, but such regulation is PTHrP signaling-independent. ..
- Hoeppner L, Secreto F, Razidlo D, Whitney T, Westendorf J. Lef1DeltaN binds beta-catenin and increases osteoblast activity and trabecular bone mass. J Biol Chem. 2011;286:10950-9 pubmed publisher..b>Lef1?N is a short isoform of Lef1 that lacks the first 113 amino acids and a well characterized high affinity ?-catenin ..
- Yu S, Zhou X, Steinke F, Liu C, Chen S, Zagorodna O, et al. The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy. Immunity. 2012;37:813-26 pubmed publisher..that TCF-1 directly repressed LEF-1 expression in early thymocytes and that conditional inactivation of Lef1 greatly delayed or prevented T cell malignancy in Tcf7(-/-) mice...
- Ito K, Lim A, Salto Tellez M, Motoda L, Osato M, Chuang L, et al. RUNX3 attenuates beta-catenin/T cell factors in intestinal tumorigenesis. Cancer Cell. 2008;14:226-37 pubmed publisher..Taken together, these data demonstrate that RUNX3 functions as a tumor suppressor by attenuating Wnt signaling. ..
- Lieven O, Ruther U. The Dkk1 dose is critical for eye development. Dev Biol. 2011;355:124-37 pubmed publisher..Therefore, our data essentially improve the knowledge of coloboma and anterior eye defects, which are common human eye developmental defects. ..
- Glass D, Bialek P, Ahn J, Starbuck M, Patel M, Clevers H, et al. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell. 2005;8:751-64 pubmed
- Kuraguchi M, Wang X, Bronson R, Rothenberg R, Ohene Baah N, Lund J, et al. Adenomatous polyposis coli (APC) is required for normal development of skin and thymus. PLoS Genet. 2006;2:e146 pubmed
- Dassule H, Lewis P, Bei M, Maas R, McMahon A. Sonic hedgehog regulates growth and morphogenesis of the tooth. Development. 2000;127:4775-85 pubmed..However, the enamel knot, a putative organizer of crown formation, is present and expresses Fgf4, Wnt10b, Bmp2 and Lef1, as in the wild type...
- Kahler R, Westendorf J. Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter. J Biol Chem. 2003;278:11937-44 pubmed..A functional binding site for the high mobility group protein lymphoid enhancer-binding factor 1 (LEF1) was found adjacent to the proximal Runx2-binding site in the osteocalcin promoter...
- Chen Y, Bei M, Woo I, Satokata I, Maas R. Msx1 controls inductive signaling in mammalian tooth morphogenesis. Development. 1996;122:3035-44 pubmed..Our results show that expression of Bone Morphogenetic Protein 4 (BMP4), the HMG box gene Lef1 and the heparan sulfate proteoglycan syndecan-1 is specifically reduced in Msx1 mutant dental mesenchyme, while ..
- Dasgupta R, Fuchs E. Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development. 1999;126:4557-68 pubmed..mice, TOPGAL expression was directly stimulated by a stabilized form of beta -catenin, but was also dependent upon LEF1/TCF3 in skin...
- Boras Granic K, Chang H, Grosschedl R, Hamel P. Lef1 is required for the transition of Wnt signaling from mesenchymal to epithelial cells in the mouse embryonic mammary gland. Dev Biol. 2006;295:219-31 pubmed..b>Lef1-mediated canonical Wnt signaling is required for morphogenesis of these skin appendages during embryogenesis...
- Chen J, Lan Y, Baek J, Gao Y, Jiang R. Wnt/beta-catenin signaling plays an essential role in activation of odontogenic mesenchyme during early tooth development. Dev Biol. 2009;334:174-85 pubmed publisher..We show that mesenchymal beta-catenin function is required for expression of Lef1 and Fgf3 in the developing tooth mesenchyme and for induction of primary enamel knot in the developing tooth ..
- St Jacques B, Dassule H, Karavanova I, Botchkarev V, Li J, Danielian P, et al. Sonic hedgehog signaling is essential for hair development. Curr Biol. 1998;8:1058-68 pubmed..Shh signaling is not required for initiating hair follicle development. Shh signaling is essential, however, for controlling ingrowth and morphogenesis of the hair follicle. ..
- Laurikkala J, Pispa J, Jung H, Nieminen P, Mikkola M, Wang X, et al. Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar. Development. 2002;129:2541-53 pubmed..and hair follicles, we analyzed the expression and regulation of Eda and Edar in wild type as well as Tabby and Lef1 mutant mouse embryos...
- Niemann C, Owens D, Hülsken J, Birchmeier W, Watt F. Expression of DeltaNLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours. Development. 2002;129:95-109 pubmedTo examine the consequences of repressing beta-catenin/Lef1 signalling in mouse epidermis, we expressed a DeltaNLef1 transgene, which lacks the beta-catenin binding site, under the control of the keratin 14 promoter...
- Sasaki T, Ito Y, Xu X, Han J, Bringas P, Maeda T, et al. LEF1 is a critical epithelial survival factor during tooth morphogenesis. Dev Biol. 2005;278:130-43 pubmedb>LEF1 is a cell-type-specific transcription factor and mediates Wnt signaling pathway by association with its co-activator beta-catenin...
- Oosterwegel M, van de Wetering M, Timmerman J, Kruisbeek A, Destree O, Meijlink F, et al. Differential expression of the HMG box factors TCF-1 and LEF-1 during murine embryogenesis. Development. 1993;118:439-48 pubmed..Postnatally, expression of both genes could only be detected in lymphoid tissues. These observations suggest that TCF-1 and LEF-1 exert differential functions during murine embryogenesis. ..
- Jamora C, DasGupta R, Kocieniewski P, Fuchs E. Links between signal transduction, transcription and adhesion in epithelial bud development. Nature. 2003;422:317-22 pubmed..signals: a Wnt protein to stabilize beta-catenin, and a bone morphogenetic protein (BMP) inhibitor to produce Lef1. Beta-catenin then binds to, and activates, Lef1 transcription complexes that appear to act uncharacteristically by ..
- Mailleux A, Spencer Dene B, Dillon C, Ndiaye D, Savona Baron C, Itoh N, et al. Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo. Development. 2002;129:53-60 pubmed..We have investigated the molecular mechanisms of mammary placode development using Lef1 as a marker for the epithelial component of the placode, and mice deficient for Fgf10 or Fgfr2b, both of which fail ..
- Fujimura N, Taketo M, Mori M, Korinek V, Kozmik Z. Spatial and temporal regulation of Wnt/beta-catenin signaling is essential for development of the retinal pigment epithelium. Dev Biol. 2009;334:31-45 pubmed publisher..Combined, our data suggest that Wnt/beta-catenin signaling plays an essential role in development of RPE by maintaining or inducing expression of Mitf and Otx2. ..
- Bluske K, Kawakami Y, Koyano Nakagawa N, Nakagawa Y. Differential activity of Wnt/beta-catenin signaling in the embryonic mouse thalamus. Dev Dyn. 2009;238:3297-309 pubmed publisher..Analysis of mice with enhanced or reduced Shh signal showed that Axin2 expression is similar to controls. These results suggest that differential Wnt signaling may play a role in patterning the thalamus independent of Shh signaling. ..
- Galceran J, Farinas I, Depew M, Clevers H, Grosschedl R. Wnt3a-/--like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice. Genes Dev. 1999;13:709-17 pubmed..However, targeted gene inactivations of Lef1, Tcf1, or Tcf4 in the mouse do not produce phenotypes that mimic any known Wnt mutation...
- Okamura R, Sigvardsson M, Galceran J, Verbeek S, Clevers H, Grosschedl R. Redundant regulation of T cell differentiation and TCRalpha gene expression by the transcription factors LEF-1 and TCF-1. Immunity. 1998;8:11-20 pubmed..Targeted gene disruption of either the Tcf1 or Lef1 gene in mice did not affect TCRalpha gene expression and resulted in an incomplete defect or no defect in thymocyte ..
- Järvinen E, Salazar Ciudad I, Birchmeier W, Taketo M, Jernvall J, Thesleff I. Continuous tooth generation in mouse is induced by activated epithelial Wnt/beta-catenin signaling. Proc Natl Acad Sci U S A. 2006;103:18627-32 pubmed..These results may implicate Wnt signaling in tooth renewal, a capacity that was all but lost when mammals evolved progressively more complicated tooth shapes. ..
- Giese K, Kingsley C, Kirshner J, Grosschedl R. Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1-induced DNA bending and multiple protein-protein interactions. Genes Dev. 1995;9:995-1008 pubmed
- Liu H, Thurig S, Mohamed O, Dufort D, Wallace V. Mapping canonical Wnt signaling in the developing and adult retina. Invest Ophthalmol Vis Sci. 2006;47:5088-97 pubmed
- Yin Y, White A, Huh S, Hilton M, Kanazawa H, Long F, et al. An FGF-WNT gene regulatory network controls lung mesenchyme development. Dev Biol. 2008;319:426-36 pubmed publisher..Together, both FGF and WNT signaling pathways function to sustain mesenchymal growth and coordinate epithelial morphogenesis during the pseudoglandular stage of lung development. ..
- Andl T, Reddy S, Gaddapara T, Millar S. WNT signals are required for the initiation of hair follicle development. Dev Cell. 2002;2:643-53 pubmed..This phenotype indicates that activation of WNT signaling in the skin precedes, and is required for, localized expression of regulatory genes and initiation of hair follicle placode formation. ..
- Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell. 2001;105:533-45 pubmed..Further analysis demonstrates that beta-catenin is essential for fate decisions of skin stem cells: in the absence of beta-catenin, stem cells fail to differentiate into follicular keratinocytes, but instead adopt an epidermal fate. ..
- Zhao H, Oka K, Bringas P, Kaartinen V, Chai Y. TGF-beta type I receptor Alk5 regulates tooth initiation and mandible patterning in a type II receptor-independent manner. Dev Biol. 2008;320:19-29 pubmed publisher..There is an intrinsic requirement for Alk5 signal in regulating the fate of CNC cells during tooth and mandible development. ..
- Fotaki V, Price D, Mason J. Wnt/?-catenin signaling is disrupted in the extra-toes (Gli3(Xt/Xt) ) mutant from early stages of forebrain development, concomitant with anterior neural plate patterning defects. J Comp Neurol. 2011;519:1640-57 pubmed publisher..Our data reveal that Gli3 is required at the neural plate stage to regulate Wnt expression and Wnt/?-catenin signaling in the presumptive forebrain and confirm its previously proposed role in patterning the anterior neural plate. ..
- Iwatsuki K, Liu H, Grónder A, Singer M, Lane T, Grosschedl R, et al. Wnt signaling interacts with Shh to regulate taste papilla development. Proc Natl Acad Sci U S A. 2007;104:2253-8 pubmed..The elimination of Wnt/beta-catenin signaling in either Lef1 or Wnt10b knockout mice resulted in down-regulation of Shh expression...
- Zhou P, Byrne C, Jacobs J, Fuchs E. Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate. Genes Dev. 1995;9:700-13 pubmed..Collectively, our findings demonstrate that ectodermal expression of LEF-1 plays a central role in gene expression, pattern formation, and other developmental processes involving epithelial-mesenchymal associations. ..
- Hecht A, Stemmler M. Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4. J Biol Chem. 2003;278:3776-85 pubmed..We found that TCF4E but not LEF1 supported beta-catenin-dependent activation of the Cdx1 promoter, whereas LEF1 specifically activated the Siamois ..
- Kobielak K, Pasolli H, Alonso L, Polak L, Fuchs E. Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA. J Cell Biol. 2003;163:609-23 pubmed..In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail ..