Genomes and Genes
Gene Symbol: Tfap2a
Description: transcription factor AP-2, alpha
Alias: AP-2, AP2alpha, Ap-2 (a), Ap2, Ap2tf, Tcfap2a, transcription factor AP-2-alpha, activating enhancer-binding protein 2 alpha, activator protein 2
- Randall V, McCue K, Roberts C, Kyriakopoulou V, Beddow S, Barrett A, et al. Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice. J Clin Invest. 2009;119:3301-10 pubmed publisher..We could not rescue PAA morphogenesis by restoring neural crest Chd7 expression. Rather, biallelic expression of Chd7 and Tbx1 in the pharyngeal ectoderm was required for normal PAA development...
- Liu W, Selever J, Wang D, Lu M, Moses K, Schwartz R, et al. Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling. Proc Natl Acad Sci U S A. 2004;101:4489-94 pubmed..Our findings uncover a previously uncharacterized function for Bmp4 in vascular remodeling of the BAAs, and they show definitively that Bmp4, in cooperation with Bmp7, has a central role in OFT septation. ..
- Brewer S, Williams T. Loss of AP-2alpha impacts multiple aspects of ventral body wall development and closure. Dev Biol. 2004;267:399-417 pubmed..These findings provide a fundamental understanding of how AP-2alpha functions in the closure of the ventral body wall, as well as offer insight into related human birth defects. ..
- Abu Issa R, Smyth G, Smoak I, Yamamura K, Meyers E. Fgf8 is required for pharyngeal arch and cardiovascular development in the mouse. Development. 2002;129:4613-25 pubmed..This study defines the cardiovascular defects present in Fgf8 mutants and supports a role for Fgf8 in development of all the pharyngeal arches and in NCC survival. ..
- Zhang J, Chang J, Huang Y, Lin X, Luo Y, Schwartz R, et al. The FGF-BMP signaling axis regulates outflow tract valve primordium formation by promoting cushion neural crest cell differentiation. Circ Res. 2010;107:1209-19 pubmed publisher..The results demonstrate a novel mechanism by which the FGF-BMP signaling axis regulates formation of OFT valve primordia by controlling smooth muscle differentiation of cushion NCCs. ..
- Pontoriero G, Deschamps P, Ashery Padan R, Wong R, Yang Y, Zavadil J, et al. Cell autonomous roles for AP-2alpha in lens vesicle separation and maintenance of the lens epithelial cell phenotype. Dev Dyn. 2008;237:602-17 pubmed publisher..wild-type littermates revealed differential expression of 415 mRNAs, including reduced expression of genes important for maintaining the lens epithelial cell phenotype, such as E-cadherin. ..
- Wang X, Bolotin D, Chu D, Polak L, Williams T, Fuchs E. AP-2alpha: a regulator of EGF receptor signaling and proliferation in skin epidermis. J Cell Biol. 2006;172:409-21 pubmed..These results provide insights into why elevated AP-2alpha levels are often associated with terminal differentiation and why tumor cells often display reduced AP-2alpha and elevated EGFR proteins. ..
- Trokovic N, Trokovic R, Mai P, Partanen J. Fgfr1 regulates patterning of the pharyngeal region. Genes Dev. 2003;17:141-53 pubmed..Our results indicate that Fgfr1 patterns the pharyngeal region to create a permissive environment for neural crest cell migration. ..
- Brewer S, Feng W, Huang J, Sullivan S, Williams T. Wnt1-Cre-mediated deletion of AP-2alpha causes multiple neural crest-related defects. Dev Biol. 2004;267:135-52 pubmed..factor is required for multiple aspects of vertebrate development and mice lacking the AP-2alpha gene (tcfap2a) die at birth from severe defects affecting the head and trunk...
- Williams T, Admon A, Luscher B, Tjian R. Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements. Genes Dev. 1988;2:1557-69 pubmed..This indicates that AP-2 may be a transcription factor involved in the control of developmentally regulated gene expression. ..
- Orso F, Jäger R, Calogero R, Schorle H, Sismondi P, De Bortoli M, et al. AP-2alpha regulates migration of GN-11 neurons via a specific genetic programme involving the Axl receptor tyrosine kinase. BMC Biol. 2009;7:25 pubmed publisher..We show that AP-2alpha plays an essential role in cell movement via the activation of cell-specific genetic programmes. Moreover, we demonstrate that the AP-2alpha regulated gene Axl is an essential player in GN-11 neuron migration. ..
- Schorle H, Meier P, Buchert M, Jaenisch R, Mitchell P. Transcription factor AP-2 essential for cranial closure and craniofacial development. Nature. 1996;381:235-8 pubmed
- Ishii M, Han J, Yen H, Sucov H, Chai Y, Maxson R. Combined deficiencies of Msx1 and Msx2 cause impaired patterning and survival of the cranial neural crest. Development. 2005;132:4937-50 pubmed..This increase in apoptosis may contribute to the mispatterning of the cranial ganglia and the hypoplasia of the first arch. ..
- Ferretti E, Li B, Zewdu R, Wells V, Hebert J, Karner C, et al. A conserved Pbx-Wnt-p63-Irf6 regulatory module controls face morphogenesis by promoting epithelial apoptosis. Dev Cell. 2011;21:627-41 pubmed publisher..Dysregulation of this network leads to localized suppression of midfacial apoptosis and CL/P. Ectopic Wnt ectodermal expression in Pbx mutants rescues the clefting, opening avenues for tissue repair. ..
- Zhang J, Brewer S, Huang J, Williams T. Overexpression of transcription factor AP-2alpha suppresses mammary gland growth and morphogenesis. Dev Biol. 2003;256:127-45 pubmed..Our studies strongly support a role for the AP-2 proteins in regulating the proliferation and differentiation of mammary gland epithelial cells in both mouse and human. ..
- Bamforth S, Braganca J, Eloranta J, Murdoch J, Marques F, Kranc K, et al. Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activator. Nat Genet. 2001;29:469-74 pubmed..As certain Tfap2 isoforms are essential in neural crest, neural tube and cardiac development, we propose that abnormal embryogenesis in mice lacking Cited2 results, at least in part, from its role as a Tfap2 co-activator. ..
- Braganca J, Eloranta J, Bamforth S, Ibbitt J, Hurst H, Bhattacharya S. Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2. J Biol Chem. 2003;278:16021-9 pubmed..p300/CBP, CITED2, and TFAP2A are essential for normal neural tube and cardiac development...
- Brewer S, Jiang X, Donaldson S, Williams T, Sucov H. Requirement for AP-2alpha in cardiac outflow tract morphogenesis. Mech Dev. 2002;110:139-49 pubmed..5. AP-2alpha may be involved in an interaction between neural crest and surrounding tissues in the subpharyngeal region, thereby promoting normal outflow tract morphogenesis. ..
- Talbot D, Loring J, Schorle H, Lorgin J. Spatiotemporal expression pattern of keratins in skin of AP-2alpha-deficient mice. J Invest Dermatol. 1999;113:816-20 pubmed..Furthermore, the mutants lack a ring of ectodermal cells highly positive for keratin 15 in the area where lens induction occurs, indicating a defect in the inductive interactions underlying eye formation. ..
- Mori Akiyama Y, Akiyama H, Rowitch D, de Crombrugghe B. Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest. Proc Natl Acad Sci U S A. 2003;100:9360-5 pubmed..and the frontonasal mass of mutant embryos was comparable to that of WT embryos, and the pattern of expression of Ap2, a marker of migrating CNC cells, was normal...
- Feng W, Williams T. Cloning and characterization of the mouse AP-2 epsilon gene: a novel family member expressed in the developing olfactory bulb. Mol Cell Neurosci. 2003;24:460-75 pubmed..A comparison of AP-2 gene family expression in the olfactory system suggests both distinct and overlapping functions for these transcription factors in forebrain development. ..
- Nelson D, Williams T. Frontonasal process-specific disruption of AP-2alpha results in postnatal midfacial hypoplasia, vascular anomalies, and nasal cavity defects. Dev Biol. 2004;267:72-92 pubmed..The characteristics of the FKO mouse model are a unique combination of midfacial growth anomalies, and provide the first evidence that AP-2alpha is essential for appropriate postnatal craniofacial morphogenesis. ..
- Zhang J, Lin Y, Zhang Y, Lan Y, Lin C, Moon A, et al. Frs2alpha-deficiency in cardiac progenitors disrupts a subset of FGF signals required for outflow tract morphogenesis. Development. 2008;135:3611-22 pubmed publisher..These results provide new insight into the signaling molecules downstream of FGF receptor tyrosine kinases in cardiac progenitors. ..
- Mitchell P, Timmons P, Hebert J, Rigby P, Tjian R. Transcription factor AP-2 is expressed in neural crest cell lineages during mouse embryogenesis. Genes Dev. 1991;5:105-19 pubmed..This embryonic expression pattern is spatially and temporally consistent with a role for AP-2 in regulating transcription of genes involved in the morphogenesis of the peripheral nervous system, face, limbs, skin, and nephric tissues. ..
- Winger Q, Huang J, Auman H, Lewandoski M, Williams T. Analysis of transcription factor AP-2 expression and function during mouse preimplantation development. Biol Reprod. 2006;75:324-33 pubmed..Four AP-2 genes are differentially expressed during the preimplantation period,Tcfap2a, Tcfap2b, Tcfap2c, and Tcfap2e...
- Kohlbecker A, Lee A, Schorle H. Exencephaly in a subset of animals heterozygous for AP-2alpha mutation. Teratology. 2002;65:213-8 pubmed..The results support a role of AP-2alpha in the etiology of exencephalic disorders. The phenotype observed might be due to a downregulation of the remaining allele suggesting the presence of an upstream modifier gene. ..
- Hilger Eversheim K, Moser M, Schorle H, Buettner R. Regulatory roles of AP-2 transcription factors in vertebrate development, apoptosis and cell-cycle control. Gene. 2000;260:1-12 pubmed
- 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. ..
- Calmont A, Ivins S, van Bueren K, Papangeli I, Kyriakopoulou V, Andrews W, et al. Tbx1 controls cardiac neural crest cell migration during arch artery development by regulating Gbx2 expression in the pharyngeal ectoderm. Development. 2009;136:3173-83 pubmed publisher..We propose that the spatiotemporal control of this tightly orchestrated network of genes participates in crucial aspects of PAA development...
- Zhang J, Hagopian Donaldson S, Serbedzija G, Elsemore J, Plehn Dujowich D, McMahon A, et al. Neural tube, skeletal and body wall defects in mice lacking transcription factor AP-2. Nature. 1996;381:238-41 pubmed..Analysis of these mice earlier in embryogenesis indicates a failure of cranial neural-tube closure and defects in cranial ganglia development. We have shown that AP-2 is a fundamental regulator of mammalian craniofacial development. ..
- Feng W, Leach S, Tipney H, Phang T, Geraci M, Spritz R, et al. Spatial and temporal analysis of gene expression during growth and fusion of the mouse facial prominences. PLoS ONE. 2009;4:e8066 pubmed publisher..Overall, our studies provide a valuable resource for probing orofacial development and a robust dataset for bioinformatic analysis of spatial and temporal gene expression changes during embryogenesis. ..
- Werling U, Schorle H. Transcription factor gene AP-2 gamma essential for early murine development. Mol Cell Biol. 2002;22:3149-56 pubmed..Therefore, AP-2 gamma seems to be required in early embryonic development because it regulates the genetic programs controlling proliferation and differentiation of extraembryonic trophectodermal cells. ..
- Boulet A, Moon A, Arenkiel B, Capecchi M. The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth. Dev Biol. 2004;273:361-72 pubmed..By using a CRE driver expressed in both forelimb and hindlimb ectoderm to inactivate Fgf4 and Fgf8, we have produced mice lacking all limbs, allowing a direct comparison of FGF requirements in the two locations. ..
- Macatee T, Hammond B, Arenkiel B, Francis L, Frank D, Moon A. Ablation of specific expression domains reveals discrete functions of ectoderm- and endoderm-derived FGF8 during cardiovascular and pharyngeal development. Development. 2003;130:6361-74 pubmed
- Wang J, Bai Y, Li H, Greene S, Klysik E, Yu W, et al. MicroRNA-17-92, a direct Ap-2? transcriptional target, modulates T-box factor activity in orofacial clefting. PLoS Genet. 2013;9:e1003785 pubmed publisher..Our data are the first genetic evidence that an individual miR or miR cluster is functionally important in mammalian CL/P. ..
- Forni P, Taylor Burds C, Melvin V, Williams T, Williams T, Wray S. Neural crest and ectodermal cells intermix in the nasal placode to give rise to GnRH-1 neurons, sensory neurons, and olfactory ensheathing cells. J Neurosci. 2011;31:6915-27 pubmed publisher..Furthermore, the results indicate that certain conditions that impact olfaction and sexual development, such as Kallmann syndrome, may be in part neurocristopathies...
- Olaopa M, Zhou H, Snider P, Wang J, Schwartz R, Moon A, et al. Pax3 is essential for normal cardiac neural crest morphogenesis but is not required during migration nor outflow tract septation. Dev Biol. 2011;356:308-22 pubmed publisher..we conditionally deleted Pax3 in both the premigratory and migratory neural crest populations via Wnt1-Cre and Ap2?-Cre and via P0-Cre in only the migratory neural crest, and compared these phenotypes to the pulmonary atresia ..
- Murdoch B, DelConte C, GarcÃa Castro M. Pax7 lineage contributions to the mammalian neural crest. PLoS ONE. 2012;7:e41089 pubmed publisher..They shed light regarding the regionally distinct phenotypes observed in Pax3 and Pax7 mutants, and provide a unique perspective into the potential roles of Pax7 during disease and development. ..
- Moore Scott B, Manley N. Differential expression of Sonic hedgehog along the anterior-posterior axis regulates patterning of pharyngeal pouch endoderm and pharyngeal endoderm-derived organs. Dev Biol. 2005;278:323-35 pubmed..Our data suggest that, as in the posterior gut endoderm, exclusion of Shh expression from developing primordia is required for the proper development of pharyngeal-derived organs. ..
- Moser M, Imhof A, Pscherer A, Bauer R, Amselgruber W, Sinowatz F, et al. Cloning and characterization of a second AP-2 transcription factor: AP-2 beta. Development. 1995;121:2779-88 pubmed..In summary, our analyses of embryonic and adult mice demonstrate that two different AP-2 transcription factors are specifically expressed during differentiation of many neural, epidermal and urogenital tissues. ..
- Moser M, Pscherer A, Roth C, Becker J, Mücher G, Zerres K, et al. Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta. Genes Dev. 1997;11:1938-48 pubmed..Sequence analyses of ARPKD patients and linkage analyses using intragenic polymorphic markers indicate that the AP-2beta gene is located in close proximity to but distinct from the ARPKD gene. ..
- Nottoli T, Hagopian Donaldson S, Zhang J, Perkins A, Williams T. AP-2-null cells disrupt morphogenesis of the eye, face, and limbs in chimeric mice. Proc Natl Acad Sci U S A. 1998;95:13714-9 pubmed
- Chang H, Huylebroeck D, Verschueren K, Guo Q, Matzuk M, Zwijsen A. Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development. 1999;126:1631-42 pubmed..Despite the expression of Smad5 from gastrulation onwards, and in contrast to knockouts of Smad2 and Smad4, Smad5 only becomes essential later in extraembryonic and embryonic development. ..
- Goddeeris M, Schwartz R, Klingensmith J, Meyers E. Independent requirements for Hedgehog signaling by both the anterior heart field and neural crest cells for outflow tract development. Development. 2007;134:1593-604 pubmed..Disruption of any of these steps can result in a single OFT phenotype. ..
- Byrne C, Tainsky M, Fuchs E. Programming gene expression in developing epidermis. Development. 1994;120:2369-83 pubmed..We show that AP2 (but not Sp1) cRNAs hybridize in a pattern similar to, but preceding that of basal keratin cRNAs...
- Freyer L, Aggarwal V, Morrow B. Dual embryonic origin of the mammalian otic vesicle forming the inner ear. Development. 2011;138:5403-14 pubmed publisher..This study defines a dual cellular origin of the inner ear from sensory placode ectoderm and NECs, and changes the current paradigm of inner ear neurosensory development. ..
- Jain R, Engleka K, Rentschler S, Manderfield L, Li L, Yuan L, et al. Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves. J Clin Invest. 2011;121:422-30 pubmed publisher..Hence, defects of cardiac neural crest can result in functionally abnormal semilunar valves and concomitant aortic arch artery abnormalities. ..
- Kramer P, Krishnamurthy R, Mitchell P, Wray S. Transcription factor activator protein-2 is required for continued luteinizing hormone-releasing hormone expression in the forebrain of developing mice. Endocrinology. 2000;141:1823-38 pubmed..These results indicate a developmentally restricted involvement of the transcription factor AP-2 in LHRH expression once the LHRH neurons have migrated into the forebrain, but before establishment of an adult-like distribution. ..
- Washington Smoak I, Byrd N, Abu Issa R, Goddeeris M, Anderson R, Morris J, et al. Sonic hedgehog is required for cardiac outflow tract and neural crest cell development. Dev Biol. 2005;283:357-72 pubmed..Our data suggest that SHH signaling does not act directly on NCCs as a survival factor, but rather acts to restrict the domains that NCCs can populate during early stages (e8.5-10.5) of cardiovascular and craniofacial development. ..
- Mesbah K, Rana M, Francou A, van Duijvenboden K, Papaioannou V, Moorman A, et al. Identification of a Tbx1/Tbx2/Tbx3 genetic pathway governing pharyngeal and arterial pole morphogenesis. Hum Mol Genet. 2012;21:1217-29 pubmed publisher..2DS patients. ..
- Klimova L, Antosova B, Kuzelova A, Strnad H, Kozmik Z. Onecut1 and Onecut2 transcription factors operate downstream of Pax6 to regulate horizontal cell development. Dev Biol. 2015;402:48-60 pubmed publisher..Taken together, this study suggests the model in which Pax6 regulates the maintenance of horizontal cells through the activation of Onecut1 and Onecut2 transcription factors. ..
- Huh S, Ornitz D. Beta-catenin deficiency causes DiGeorge syndrome-like phenotypes through regulation of Tbx1. Development. 2010;137:1137-47 pubmed publisher..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...
- Moon A, Guris D, Seo J, Li L, Hammond J, Talbot A, et al. Crkl deficiency disrupts Fgf8 signaling in a mouse model of 22q11 deletion syndromes. Dev Cell. 2006;10:71-80 pubmed..These findings provide mechanistic insight into disrupted intercellular interactions in the pathogenesis of malformations seen in del22q11 syndrome. ..
- Zhou H, Wang J, Rogers R, Conway S. Lineage-specific responses to reduced embryonic Pax3 expression levels. Dev Biol. 2008;315:369-82 pubmed publisher..Thus, we have established that there are different minimum threshold requirements for Pax3 within different Pax3-expressing lineages. ..
- Guo W, Chen J, Yang Y, Zhu J, Wu J. Epigenetic programming of Dnmt3a mediated by AP2Î± is required for granting preadipocyte the ability to differentiate. Cell Death Dis. 2016;7:e2496 pubmed publisher..We further identified that the expression of Activator protein 2Î± (AP2Î±), a member of the transcription factor activator protein 2 (AP2) family, was highly correlated ..
- Zhao F, Franco H, Rodriguez K, Brown P, Tsai M, Tsai S, et al. Elimination of the male reproductive tract in the female embryo is promoted by COUP-TFII in mice. Science. 2017;357:717-720 pubmed publisher..We thus suggest that elimination of Wolffian ducts in female embryos is actively promoted by COUP-TFII, which suppresses a mesenchyme-epithelium cross-talk responsible for Wolffian duct maintenance. ..