Genomes and Genes
Gene Symbol: En1
Description: engrailed 1
Alias: En-1, Mo-en.1, engrailed-1, homeobox protein engrailed-1, homeobox protein en-1, mo-En-1
- Stettler O, Joshi R, Wizenmann A, Reingruber J, Holcman D, Bouillot C, et al. Engrailed homeoprotein recruits the adenosine A1 receptor to potentiate ephrin A5 function in retinal growth cones. Development. 2012;139:215-24 pubmed publisherb>Engrailed 1 and engrailed 2 homeoprotein transcription factors (collectively Engrailed) display graded expression in the chick optic tectum where they participate in retino-tectal patterning...
- Pierani A, Brenner Morton S, Chiang C, Jessell T. A sonic hedgehog-independent, retinoid-activated pathway of neurogenesis in the ventral spinal cord. Cell. 1999;97:903-15 pubmed..analysis of the induction of ventral progenitors that express the Dbx homeodomain proteins and of Evx1/2 (V0) and En1 (V1) neurons...
- Simon H, Saueressig H, Wurst W, Goulding M, O Leary D. Fate of midbrain dopaminergic neurons controlled by the engrailed genes. J Neurosci. 2001;21:3126-34 pubmed..However, the engrailed genes control the survival of midbrain dopaminergic neurons in a gene dose-dependent manner. Our findings also suggest a link between engrailed and Parkinson's disease. ..
- Burrill J, Moran L, Goulding M, Saueressig H. PAX2 is expressed in multiple spinal cord interneurons, including a population of EN1+ interneurons that require PAX6 for their development. Development. 1997;124:4493-503 pubmed..of PAX2-expressing interneurons in the spinal cord are marked by coexpression of the transcription factors, EN1 and EVX1...
- Ding J, Yang L, Yan Y, Chen A, Desai N, Wynshaw Boris A, et al. Cripto is required for correct orientation of the anterior-posterior axis in the mouse embryo. Nature. 1998;395:702-7 pubmed..Our results indicate that Cripto signalling is essential for the conversion of a proximal-distal asymmetry into an orthogonal anterior-posterior axis. ..
- Yang J, Brown A, Ellisor D, Paul E, Hagan N, Zervas M. Dynamic temporal requirement of Wnt1 in midbrain dopamine neuron development. Development. 2013;140:1342-52 pubmed publisher..Interestingly, an En1-derived domain persists after the early deletion of Wnt1 and mutant cells express OTX2...
- Blak A, Naserke T, Weisenhorn D, Prakash N, Partanen J, Wurst W. Expression of Fgf receptors 1, 2, and 3 in the developing mid- and hindbrain of the mouse. Dev Dyn. 2005;233:1023-30 pubmed..Fgfr3 expression is in contact with the Fgf8 expression domain only in the rostroventral hindbrain. Based on these findings, we postulate a role for FGFR2 and FGFR3 in FGF signaling in the ventral midbrain and hindbrain. ..
- Machold R, Fishell G. Math1 is expressed in temporally discrete pools of cerebellar rhombic-lip neural progenitors. Neuron. 2005;48:17-24 pubmed..Thus, we demonstrate that the cerebellar rhombic lip gives rise to multiple cell types within rhombomere 1. ..
- Omodei D, Acampora D, Mancuso P, Prakash N, Di Giovannantonio L, Wurst W, et al. Anterior-posterior graded response to Otx2 controls proliferation and differentiation of dopaminergic progenitors in the ventral mesencephalon. Development. 2008;135:3459-70 pubmed publisher..Thus, our data provide new insights into the mechanism of mesDA neuron specification and suggest Otx2 as a potential target for cell replacement-based therapeutic approaches in PD. ..
- Saueressig H, Burrill J, Goulding M. Engrailed-1 and netrin-1 regulate axon pathfinding by association interneurons that project to motor neurons. Development. 1999;126:4201-12 pubmed..By targeting the axonal reporter gene &tgr;-lacZ to the En1 locus, we show the cell-type-specific transcription factor Engrailed-1 (EN1) defines a population of association ..
- Sgaier S, Millet S, Villanueva M, Berenshteyn F, Song C, Joyner A. Morphogenetic and cellular movements that shape the mouse cerebellum; insights from genetic fate mapping. Neuron. 2005;45:27-40 pubmed..Thus, we show that progressive changes in the axes of the cerebellum underlie its genesis. ..
- Panhuysen M, Vogt Weisenhorn D, Blanquet V, Brodski C, Heinzmann U, Beisker W, et al. Effects of Wnt1 signaling on proliferation in the developing mid-/hindbrain region. Mol Cell Neurosci. 2004;26:101-11 pubmed..into Wnt1 function in the mid-/hindbrain region, we ectopically expressed Wnt1 under the control of the endogenous En1 promoter, thereby extending Wnt1 expression rostrally into the anterior midbrain and caudally into rhombomere 1...
- Di Salvio M, Di Giovannantonio L, Acampora D, Prosperi R, Omodei D, Prakash N, et al. Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP. Nat Neurosci. 2010;13:1481-8 pubmed publisher..These findings indicate that Otx2 is required to specify neuron subtype identity in VTA and may antagonize vulnerability to the Parkinsonian toxin MPTP. ..
- Adamska M, MacDonald B, Sarmast Z, Oliver E, Meisler M. En1 and Wnt7a interact with Dkk1 during limb development in the mouse. Dev Biol. 2004;272:134-44 pubmed..The extra digits and expanded apical ectodermal ridge (AER) of Dkk1-deficient mice closely resemble En1 null mice...
- Wurst W, Auerbach A, Joyner A. Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum. Development. 1994;120:2065-75 pubmed..The results of these studies suggest a cell autonomous role for En-1 in generation and/or survival of mid-hindbrain precursor cells and also a non-cell autonomous role in signalling normal development of the limbs and possibly sternum. ..
- Matise M, Joyner A. Expression patterns of developmental control genes in normal and Engrailed-1 mutant mouse spinal cord reveal early diversity in developing interneurons. J Neurosci. 1997;17:7805-16 pubmed..Rather, it is suggested that En-1 may function to distinguish a subset of interneurons during the later maturation of the spinal cord. ..
- Maatouk D, Choi K, Bouldin C, Harfe B. In the limb AER Bmp2 and Bmp4 are required for dorsal-ventral patterning and interdigital cell death but not limb outgrowth. Dev Biol. 2009;327:516-23 pubmed publisher..Investigation of Engrailed-1 (En1) expression in the AER of limb buds in which Bmp2 and Bmp4 had been removed indicated that En1 expression was ..
- Fox S, Deneris E. Engrailed is required in maturing serotonin neurons to regulate the cytoarchitecture and survival of the dorsal raphe nucleus. J Neurosci. 2012;32:7832-42 pubmed publisher..An unresolved question is whether En plays intrinsic roles in these neurons. Here, we show that En1 and En2 are expressed in maturing 5-HT neurons that will form the dorsal raphe nucleus (DRN) and part of the median ..
- Jacobs F, Veenvliet J, Almirza W, Hoekstra E, von Oerthel L, van der Linden A, et al. Retinoic acid-dependent and -independent gene-regulatory pathways of Pitx3 in meso-diencephalic dopaminergic neurons. Development. 2011;138:5213-22 pubmed publisher..RA signaling represents only one aspect of the Pitx3 downstream cascade, as Vmat2, Dat, Ahd2 (Aldh1a1), En1, En2 and Cck were unaffected by RA treatment and are (subset) specifically modulated by Pitx3...
- Peng C, Li N, Ng Y, Zhang J, Meier F, Theis F, et al. A unilateral negative feedback loop between miR-200 microRNAs and Sox2/E2F3 controls neural progenitor cell-cycle exit and differentiation. J Neurosci. 2012;32:13292-308 pubmed..The lack of a negative regulation of Sox2 and E2F3 by miR-200 in conditional Dicer1 mutants (En1(+/Cre); Dicer1(flox/flox) mice) and after miR-200 knockdown in vitro leads to a strongly reduced cell-cycle exit ..
- Barrow J, Thomas K, Boussadia Zahui O, Moore R, Kemler R, Capecchi M, et al. Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge. Genes Dev. 2003;17:394-409 pubmed..Finally, we demonstrate that Wnt/beta-catenin signaling lies upstream of the Bmp signaling pathway in establishment of the AER and regulation of the dorsoventral polarity of the limb. ..
- Rhinn M, Dierich A, Shawlot W, Behringer R, Le Meur M, Ang S. Sequential roles for Otx2 in visceral endoderm and neuroectoderm for forebrain and midbrain induction and specification. Development. 1998;125:845-56 pubmed..Altogether, these results demonstrate that Otx2 is first required in the visceral endoderm for the induction, and subsequently in the neuroectoderm for the specification of forebrain and midbrain territories. ..
- Wizenmann A, Brunet I, Lam J, Sonnier L, Beurdeley M, Zarbalis K, et al. Extracellular Engrailed participates in the topographic guidance of retinal axons in vivo. Neuron. 2009;64:355-366 pubmed publisher..Collectively, our results indicate that extracellular Engrailed contributes to retinotectal mapping in vivo by modulating the sensitivity of growth cones to EphrinA. ..
- Dhande O, Bhatt S, Anishchenko A, Elstrott J, Iwasato T, Swindell E, et al. Role of adenylate cyclase 1 in retinofugal map development. J Comp Neurol. 2012;520:1562-83 pubmed publisher..These results suggest that AC1 in RGC axons mediates the development of retinotopy and eye-specific segregation in the SC and dorsal LGN. ..
- Sgadò P, Alberi L, Gherbassi D, Galasso S, Ramakers G, Alavian K, et al. Slow progressive degeneration of nigral dopaminergic neurons in postnatal Engrailed mutant mice. Proc Natl Acad Sci U S A. 2006;103:15242-7 pubmed..this requirement, the cells die by apoptosis when all four alleles of the Engrailed genes are genetically ablated (En1-/-;En2-/-)...
- Wilson S, Kalinovsky A, Orvis G, Joyner A. Spatially restricted and developmentally dynamic expression of engrailed genes in multiple cerebellar cell types. Cerebellum. 2011;10:356-72 pubmed publisher..As a means to understand how the En genes regulate multiple levels of cerebellum construction, we characterized En1 and En2 expression around birth and at postnatal day (P) 21 during the period when the cerebellum undergoes a ..
- Hermanson E, Joseph B, Castro D, Lindqvist E, Aarnisalo P, Wallén A, et al. Nurr1 regulates dopamine synthesis and storage in MN9D dopamine cells. Exp Cell Res. 2003;288:324-34 pubmed..Together, the results provide evidence indicating an instructive role for Nurr1 in controlling DA synthesis and storage. ..
- Varlet I, Collignon J, Robertson E. nodal expression in the primitive endoderm is required for specification of the anterior axis during mouse gastrulation. Development. 1997;124:1033-44 pubmed..Thus we conclude that the action of nodal, a TGFbeta-related growth factor expressed in the primitive endoderm, is critical for patterning of the anterior aspects of the A-P axis. ..
- Acampora D, Avantaggiato V, Tuorto F, Simeone A. Genetic control of brain morphogenesis through Otx gene dosage requirement. Development. 1997;124:3639-50 pubmed
- Acampora D, Avantaggiato V, Tuorto F, Briata P, Corte G, Simeone A. Visceral endoderm-restricted translation of Otx1 mediates recovery of Otx2 requirements for specification of anterior neural plate and normal gastrulation. Development. 1998;125:5091-104 pubmed..Moreover, our data lead us to hypothesize that the differential post-transcriptional control existing between VE and epiblast cells may potentially contribute to fundamental regulatory mechanisms required for head specification. ..
- Davis C, Holmyard D, Millen K, Joyner A. Examining pattern formation in mouse, chicken and frog embryos with an En-specific antiserum. Development. 1991;111:287-98 pubmed..The results show that En expression is a good marker for pattern formation in a variety of tissues and will be useful in experimental studies designed to characterize further these processes. ..
- Lin W, Metzakopian E, Mavromatakis Y, Gao N, Balaskas N, Sasaki H, et al. Foxa1 and Foxa2 function both upstream of and cooperatively with Lmx1a and Lmx1b in a feedforward loop promoting mesodiencephalic dopaminergic neuron development. Dev Biol. 2009;333:386-96 pubmed publisher..Our data therefore provide new insights into the specification and differentiation of mesodiencephalic dopaminergic neurons and identifies Foxa1 and Foxa2 as essential regulators in these processes. ..
- Soshnikova N, Zechner D, Huelsken J, Mishina Y, Behringer R, Taketo M, et al. Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb. Genes Dev. 2003;17:1963-8 pubmed..Thus, AER formation and dorsal-ventral patterning of limbs are tightly controlled by an intricate interplay between Wnt/beta-catenin and BMP receptor signaling. ..
- Chen D, Jarrell A, Guo C, Lang R, Atit R. Dermal ?-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation. Development. 2012;139:1522-33 pubmed publisher..These data reveal functional roles for dermal Wnt signaling/?-catenin in fibroblast proliferation and in the epidermal hair follicle initiation program. ..
- Shawlot W, Behringer R. Requirement for Lim1 in head-organizer function. Nature. 1995;374:425-30 pubmed..A partial secondary axis developed anteriorly in some mutant embryos. Lim1 is thus an essential regulator of the vertebrate head organizer. ..
- Liu A, Losos K, Joyner A. FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate. Development. 1999;126:4827-38 pubmed..We show here that FGF8b-soaked beads can not only induce expression of the mid/hindbrain genes En1, En2 and Pax5 in mouse embryonic day 9.5 (E9...
- Kimmel R, Turnbull D, Blanquet V, Wurst W, Loomis C, Joyner A. Two lineage boundaries coordinate vertebrate apical ectodermal ridge formation. Genes Dev. 2000;14:1377-89 pubmed..One border is transient and at the limit of expression of the ventral gene En1, which corresponds to the D/V midline of the AER, and the second border corresponds to the dorsal AER margin...
- Peng C, Yajima H, Burns C, Zon L, Sisodia S, Pfaff S, et al. Notch and MAML signaling drives Scl-dependent interneuron diversity in the spinal cord. Neuron. 2007;53:813-27 pubmed..Thus, our study provides insight into the cell-extrinsic signaling that controls combinatorial transcription factor profiles involved in regulating the process of interneuron subtype diversification. ..
- Li J, Lao Z, Joyner A. Changing requirements for Gbx2 in development of the cerebellum and maintenance of the mid/hindbrain organizer. Neuron. 2002;36:31-43 pubmed..Our work has uncovered distinct requirements for Gbx2 during cerebellum formation and provided a model for how a transcription factor can play multiple roles during development. ..
- Cygan J, Johnson R, McMahon A. Novel regulatory interactions revealed by studies of murine limb pattern in Wnt-7a and En-1 mutants. Development. 1997;124:5021-32 pubmed..Unlike the normal AER, ectopic AER formation is dependent upon Wnt-7a activity, indicating that distinct genetic mechanisms may be involved in primary and secondary AER formation. ..
- Srinivas S, Watanabe T, Lin C, William C, Tanabe Y, Jessell T, et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev Biol. 2001;1:4 pubmed..them with transgenic strains expressing Cre in a ubiquitous (beta-actin-Cre) or a cell-specific (Isl1-Cre and En1-Cre) pattern...
- Alberi L, Sgadò P, Simon H. Engrailed genes are cell-autonomously required to prevent apoptosis in mesencephalic dopaminergic neurons. Development. 2004;131:3229-36 pubmed..The homeobox transcription factors engrailed 1 and engrailed 2 are expressed by this neuronal population from early in development to adulthood...
- Rowitch D, McMahon A. Pax-2 expression in the murine neural plate precedes and encompasses the expression domains of Wnt-1 and En-1. Mech Dev. 1995;52:3-8 pubmed..Pax-5 expression commences later, at the 3-somite stage. Thus, the spatial and temporal expression of Pax-2 is consistent with a possible regulatory role in the activation of Wnt-1 and En-1. ..
- Morikawa Y, Hisaoka T, Senba E. Characterization of Foxp2-expressing cells in the developing spinal cord. Neuroscience. 2009;162:1150-62 pubmed publisher..staining for Foxp2 with some homeodomain transcription factors revealed that Foxp2-expressing neurons were Pax2(+), En1(+), Evx1(-), Chx10(-), Gata3(-), and Lhx3(-) V1 interneurons in the intermediate zone throughout the ventral spinal ..
- Ahn K, Mishina Y, Hanks M, Behringer R, Crenshaw E. BMPR-IA signaling is required for the formation of the apical ectodermal ridge and dorsal-ventral patterning of the limb. Development. 2001;128:4449-61 pubmed..Along the dorsal/ventral axis, loss of engrailed 1 (En1) expression in the non-ridge ectoderm of the mutants resulted in a dorsal transformation of the ventral ..
- Liu A, Joyner A. EN and GBX2 play essential roles downstream of FGF8 in patterning the mouse mid/hindbrain region. Development. 2001;128:181-91 pubmed..5 diencephalic and midbrain explants treated with FGF8-soaked beads. By examining gene expression in En1/2 double mutant mouse embryos, we found that Fgf8, Wnt1 and Pax5 do not require the En genes for initiation of ..
- Hanks M, Wurst W, Anson Cartwright L, Auerbach A, Joyner A. Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2. Science. 1995;269:679-82 pubmed..This rescued all En-1 mutant defects, demonstrating that the difference between En-1 and En-2 stems from their divergent expression patterns. ..
- Chi C, Martinez S, Wurst W, Martin G. The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum. Development. 2003;130:2633-44 pubmed..remarkably similar pattern of cell death in Wnt1 null homozygotes, and also detected ectopic mes/met cell death in En1 null homozygotes...
- Simon H, Scholz C, O Leary D. Engrailed genes control developmental fate of serotonergic and noradrenergic neurons in mid- and hindbrain in a gene dose-dependent manner. Mol Cell Neurosci. 2005;28:96-105 pubmed..An almost identical phenotype is found in mutant mice null for Wnt1, indicating that the engrailed genes provide essential positional information for the development of the two nuclei during early embryogenesis. ..
- Ono Y, Nakatani T, Sakamoto Y, Mizuhara E, Minaki Y, Kumai M, et al. Differences in neurogenic potential in floor plate cells along an anteroposterior location: midbrain dopaminergic neurons originate from mesencephalic floor plate cells. Development. 2007;134:3213-25 pubmed..Our data provide insights into the mechanisms of specification and generation of mesDA neurons, and illustrate a useful cell replacement approach for Parkinson's disease. ..
- Brodski C, Weisenhorn D, Signore M, Sillaber I, Oesterheld M, Broccoli V, et al. Location and size of dopaminergic and serotonergic cell populations are controlled by the position of the midbrain-hindbrain organizer. J Neurosci. 2003;23:4199-207 pubmed..In addition, our data suggest that the position of the MHO during embryogenesis can modulate adult locomotor activity. ..
- Basson M, Echevarria D, Ahn C, Sudarov A, Joyner A, Mason I, et al. Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development. Development. 2008;135:889-98 pubmed publisher..We suggest a molecular explanation for this phenomenon by providing evidence that FGF signaling functions to inhibit the BMP signaling that promotes roof plate development. ..
- Kraus P, Fraidenraich D, Loomis C. Some distal limb structures develop in mice lacking Sonic hedgehog signaling. Mech Dev. 2001;100:45-58 pubmed..Finally, we show that Shh is also required for outgrowth of the limb ectoderm and thus for the formation of a distinct limb compartment. ..
- Ferri A, Lin W, Mavromatakis Y, Wang J, Sasaki H, Whitsett J, et al. Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner. Development. 2007;134:2761-9 pubmed..Subsequently, Foxa1 and Foxa2 regulate the expression of Nurr1 (Nr4a2) and engrailed 1 in immature neurons and the expression of aromatic l-amino acid decarboxylase and tyrosine hydroxylase in ..
- Logan C, Wizenmann A, Drescher U, Monschau B, Bonhoeffer F, Lumsden A. Rostral optic tectum acquires caudal characteristics following ectopic engrailed expression. Curr Biol. 1996;6:1006-14 pubmed
- Sillitoe R, Vogel M, Joyner A. Engrailed homeobox genes regulate establishment of the cerebellar afferent circuit map. J Neurosci. 2010;30:10015-24 pubmed publisher..Indeed, we discovered that En1/2 are necessary for the precise targeting of mossy fibers to distinct lobules, as well as their subsequent ..
- Treichel D, Schock F, Jackle H, Gruss P, Mansouri A. mBtd is required to maintain signaling during murine limb development. Genes Dev. 2003;17:2630-5 pubmed..The data indicate that mBtd represents a novel key player mediating proximodistal outgrowth of the limb. ..
- Ye W, Bouchard M, Stone D, Liu X, Vella F, Lee J, et al. Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8. Nat Neurosci. 2001;4:1175-81 pubmed..A network of transcription and secreted factors, including En1, Otx2, Gbx2, Grg4 and Wnt1&4, that is established independently of Pax2, further refines the expression domain ..
- Gemel J, Jacobsen C, MacArthur C. Fibroblast growth factor-8 expression is regulated by intronic engrailed and Pbx1-binding sites. J Biol Chem. 1999;274:6020-6 pubmed..In addition, in vitro mutagenesis of both Engrailed and Pbx1 sites indicated that other unidentified sites are responsible for the transcriptional enhancement observed with the intronic fragment. ..
- Xu X, Weinstein M, Li C, Naski M, Cohen R, Ornitz D, et al. Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development. 1998;125:753-65 pubmed
- Selever J, Liu W, Lu M, Behringer R, Martin J. Bmp4 in limb bud mesoderm regulates digit pattern by controlling AER development. Dev Biol. 2004;276:268-79 pubmed..Our data show that Bmp4 in limb mesoderm regulates AER induction and maturation and implicate signaling from the AER in regulation of digit number and identity. ..
- Moran Rivard L, Kagawa T, Saueressig H, Gross M, Burrill J, Goulding M. Evx1 is a postmitotic determinant of v0 interneuron identity in the spinal cord. Neuron. 2001;29:385-99 pubmed..V1 classes of ventral interneurons are defined by expression of the homeodomain transcription factors Evx1/2 and En1, respectively...
- Liu P, Wakamiya M, Shea M, Albrecht U, Behringer R, Bradley A. Requirement for Wnt3 in vertebrate axis formation. Nat Genet. 1999;22:361-5 pubmed..These studies provide genetic proof for the requirement of Wnt3 in primary axis formation in the mouse. ..
- Pfaff S, Mendelsohn M, Stewart C, Edlund T, Jessell T. Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation. Cell. 1996;84:309-20 pubmed..A population of interneurons that express Engrailed1 (EN1), however, also fails to differentiate in Isl1 mutant embryos...
- Ang S, Rossant J. HNF-3 beta is essential for node and notochord formation in mouse development. Cell. 1994;78:561-74 pubmed..HNF-3 beta is not required for the development of definitive endoderm cells, but foregut morphogenesis is severely affected in HNF-3 beta -/- embryos. ..