Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 8 March 1991:
Vol. 251. no. 4998, pp. 1239 - 1243
DOI: 10.1126/science.1672471
Prev | Table of Contents | Next

Articles

Science, Vol 251, Issue 4998, 1239-1243
Copyright © 1991 by American Association for the Advancement of Science

articles

Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox

AL Joyner, K Herrup, BA Auerbach, CA Davis, and J Rossant

Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

The two mouse genes, En-1 and En-2, that are homologs of the Drosophila segmentation gene engrailed, show overlapping spatially restricted patterns of expression in the neural tube during embryogenesis, suggestive of a role in regional specification. Mice homozygous for a targeted mutation that deletes the homeobox were viable and showed no obvious defects in embryonic development. This may be due to functional redundancy of En-2 and the related En-1 gene product during embryogenesis. Consistent with this hypothesis, the mutant mice showed abnormal foliation in the adult cerebellum, where En-2, and not En-1, is normally expressed.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Engrailed Homeobox Genes Determine the Organization of Purkinje Cell Sagittal Stripe Gene Expression in the Adult Cerebellum.
R. V. Sillitoe, D. Stephen, Z. Lao, and A. L. Joyner (2008)
J. Neurosci. 28, 12150-12162
   Abstract »    Full Text »    PDF »
Genetic subdivision of the tectum and cerebellum into functionally related regions based on differential sensitivity to engrailed proteins.
S. K. Sgaier, Z. Lao, M. P. Villanueva, F. Berenshteyn, D. Stephen, R. K. Turnbull, and A. L. Joyner (2007)
Development 134, 2325-2335
   Abstract »    Full Text »    PDF »
Progressive Loss of Dopaminergic Neurons in the Ventral Midbrain of Adult Mice Heterozygote for Engrailed1.
L. Sonnier, G. Le Pen, A. Hartmann, J.-C. Bizot, F. Trovero, M.-O. Krebs, and A. Prochiantz (2007)
J. Neurosci. 27, 1063-1071
   Abstract »    Full Text »    PDF »
Slow progressive degeneration of nigral dopaminergic neurons in postnatal Engrailed mutant mice.
P. Sgado, L. Alberi, D. Gherbassi, S. L. Galasso, G. M. J. Ramakers, K. N. Alavian, M. P. Smidt, R. H. Dyck, and H. H. Simon (2006)
PNAS 103, 15242-15247
   Abstract »    Full Text »    PDF »
Genetic basis of Joubert syndrome and related disorders of cerebellar development.
C. M. Louie and J. G. Gleeson (2005)
Hum. Mol. Genet. 14, R235-R242
   Abstract »    Full Text »    PDF »
Identification of Pax2-regulated genes by expression profiling of the mid-hindbrain organizer region.
M. Bouchard, D. Grote, S. E. Craven, Q. Sun, P. Steinlein, and M. Busslinger (2005)
Development 132, 2633-2643
   Abstract »    Full Text »    PDF »
No association between the EN2 gene and autistic disorder.
H Zhong, F J Serajee, R Nabi, and A H M M. Huq (2003)
J. Med. Genet. 40, e4-4
   Full Text »    PDF »
Distinct regulatory cascades for head and trunk myogenesis.
R. C. Mootoosamy and S. Dietrich (2002)
Development 129, 573-583
   Abstract »    Full Text »    PDF »
Genetic Control of the Mouse Cerebellum: Identification of Quantitative Trait Loci Modulating Size and Architecture.
D. C. Airey, L. Lu, and R. W. Williams (2001)
J. Neurosci. 21, 5099-5109
   Abstract »    Full Text »    PDF »
The Yeast Protein Interaction Network Evolves Rapidly and Contains Few Redundant Duplicate Genes.
A. Wagner (2001)
Mol. Biol. Evol. 18, 1283-1292
   Abstract »    Full Text »    PDF »
The Neuronal Microtubule-Associated Protein 1B Is under Homeoprotein Transcriptional Control.
M. L. Montesinos, I. Foucher, M. Conradt, G. Mainguy, L. Robel, A. Prochiantz, and M. Volovitch (2001)
J. Neurosci. 21, 3350-3359
   Abstract »    Full Text »    PDF »
Fate of Midbrain Dopaminergic Neurons Controlled by the Engrailed Genes.
H. H. Simon, H. Saueressig, W. Wurst, M. D. Goulding, and D. D. M. O'Leary (2001)
J. Neurosci. 21, 3126-3134
   Abstract »    Full Text »    PDF »
The Role of Population Size, Pleiotropy and Fitness Effects of Mutations in the Evolution of Overlapping Gene Functions.
A. Wagner (2000)
Genetics 154, 1389-1401
   Abstract »    Full Text »
Ectopic engrailed 1 expression in the dorsal midline causes cell death, abnormal differentiation of circumventricular organs and errors in axonal pathfinding.
A Louvi and M Wassef (2000)
Development 127, 4061-4071
   Abstract »    PDF »
Pax2 and homeodomain proteins cooperatively regulate a 435 bp enhancer of the mouse Pax5 gene at the midbrain-hindbrain boundary.
P. Pfeffer, M Bouchard, and M Busslinger (2000)
Development 127, 1017-1028
   Abstract »    PDF »
Fibroblast Growth Factor-8 Expression Is Regulated by Intronic Engrailed and Pbx1-binding Sites.
J. Gemel, C. Jacobsen, and C. A. MacArthur (1999)
J. Biol. Chem. 274, 6020-6026
   Abstract »    Full Text »    PDF »
Graded interference with FGF signalling reveals its dorsoventral asymmetry at the mid-hindbrain boundary.
M Carl and J Wittbrodt (1999)
Development 126, 5659-5667
   Abstract »    PDF »
FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate.
A Liu, K Losos, and A. Joyner (1999)
Development 126, 4827-4838
   Abstract »    PDF »
The midbrain-hindbrain boundary genetic cascade is activated ectopically in the diencephalon in response to the widespread expression of one of its components, the medaka gene Ol-eng2.
F Ristoratore, M Carl, K Deschet, L Richard-Parpaillon, D Boujard, J Wittbrodt, D Chourrout, F Bourrat, and J. Joly (1999)
Development 126, 3769-3779
   Abstract »    PDF »
Sequential roles for Fgf4, En1 and Fgf8 in specification and regionalisation of the midbrain.
H Shamim, R Mahmood, C Logan, P Doherty, A Lumsden, and I Mason (1999)
Development 126, 945-959
   Abstract »    PDF »
Drosophila engrailed can substitute for mouse Engrailed1 function in mid-hindbrain, but not limb development.
M. Hanks, C. Loomis, E Harris, C. Tong, L Anson-Cartwright, A Auerbach, and A Joyner (1998)
Development 125, 4521-4530
   Abstract »    PDF »
Mouse Zic1 Is Involved in Cerebellar Development.
J. Aruga, O. Minowa, H. Yaginuma, J. Kuno, T. Nagai, T. Noda, and K. Mikoshiba (1998)
J. Neurosci. 18, 284-293
   Abstract »    Full Text »    PDF »
Conserved biological function between Pax-2 and Pax-5 in midbrain and cerebellum development: Evidence from targeted mutations.
M. Schwarz, G. Alvarez-Bolado, P. Urbanek, M. Busslinger, and P. Gruss (1997)
PNAS 94, 14518-14523
   Abstract »    Full Text »    PDF »
Pattern Deformities and Cell Loss in Engrailed-2 Mutant Mice Suggest Two Separate Patterning Events during Cerebellar Development.
B. Kuemerle, H. Zanjani, A. Joyner, and K. Herrup (1997)
J. Neurosci. 17, 7881-7889
   Abstract »    Full Text »    PDF »
Tenascin-C expression in normal, inflamed, and scarred human corneas.
H Maseruka, R E Bonshek, and A B Tullo (1997)
Br J Ophthalmol 81, 677-682
   Abstract »    Full Text »    PDF »
Mmot1, a New Helix-Loop-Helix Transcription Factor Gene Displaying a Sharp Expression Boundary in the Embryonic Mouse Brain.
N. Malgaretti, O. Pozzoli, A. Bosetti, A. Corradi, S. Ciarmatori, M. Panigada, M. E. Bianchi, S. Martinez, and G. G. Consalez (1997)
J. Biol. Chem. 272, 17632-17639
   Abstract »    Full Text »    PDF »
Cooperation of Pax2 and Pax5 in midbrain and cerebellum development.
P. Urbanek, I. Fetka, M. H. Meisler, and M. Busslinger (1997)
PNAS 94, 5703-5708
   Abstract »    Full Text »    PDF »
Changing intestinal connective tissue interactions alters homeobox gene expression in epithelial cells.
I Duluc, O Lorentz, C Fritsch, C Leberquier, M Kedinger, and J. Freund (1997)
J. Cell Sci. 110, 1317-1324
   Abstract »    PDF »
The role of Engrailed in establishing the dorsoventral axis of the chick limb.
C Logan, A Hornbruch, I Campbell, and A Lumsden (1997)
Development 124, 2317-2324
   Abstract »    PDF »
Cell Interactions in Patterning the Mammalian Midbrain.
D.H. Rowitch, P.S. Danielian, S.M.K. Lee, Y. Echelard, and A.P. McMahon (1997)
Cold Spring Harb Symp Quant Biol 62, 535-544
   Abstract »    PDF »
Retroviral Misexpression of engrailed Genes in the Chick Optic Tectum Perturbs the Topographic Targeting of Retinal Axons.
G. C. Friedman and D. D. M. O'Leary (1996)
J. Neurosci. 16, 5498-5509
   Abstract »    Full Text »    PDF »
Redundant control of Ultrabithorax by zeste involves functional levels of zeste protein binding at the Ultrabithorax promoter.
J. Laney and M. Biggin (1996)
Development 122, 2303-2311
   Abstract »    PDF »
A genetic screen for mutations affecting embryogenesis in zebrafish.
W Driever, L Solnica-Krezel, A. Schier, S. Neuhauss, J Malicki, D. Stemple, D. Stainier, F Zwartkruis, S Abdelilah, Z Rangini, et al. (1996)
Development 123, 37-46
   Abstract »    PDF »
Mutations affecting the development of the embryonic zebrafish brain.
A. Schier, S. Neuhauss, M Harvey, J Malicki, L Solnica-Krezel, D. Stainier, F Zwartkruis, S Abdelilah, D. Stemple, Z Rangini, et al. (1996)
Development 123, 165-178
   Abstract »    PDF »
Genetic dissection of the retinotectal projection.
H Baier, S Klostermann, T Trowe, R. Karlstrom, C Nusslein-Volhard, and F Bonhoeffer (1996)
Development 123, 415-425
   Abstract »    PDF »
Pax2 contributes to inner ear patterning and optic nerve trajectory.
M Torres, E Gomez-Pardo, and P Gruss (1996)
Development 122, 3381-3391
   Abstract »    PDF »
Two Pax-binding sites are required for early embryonic brain expression of an Engrailed-2 transgene.
D. Song, G Chalepakis, P Gruss, and A. Joyner (1996)
Development 122, 627-635
   Abstract »    PDF »
Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain..
M Qiu, A Bulfone, S Martinez, J J Meneses, K Shimamura, R A Pedersen, and J L Rubenstein (1995)
Genes & Dev. 9, 2523-2538
   Abstract »    PDF »
Organization and promoter analysis of the mouse dishevelled-1 gene..
N Lijam and D J Sussman (1995)
Genome Res. 5, 116-124
   Abstract »    PDF »
Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2.
M Hanks, W Wurst, L Anson-Cartwright, A. Auerbach, and A. Joyner (1995)
Science 269, 679-682
   Abstract »    PDF »
Presence of isl-1-related LIM Domain Homeobox Genes in Teleost and Their Similar Patterns of Expression in Brain and Spinal Cord.
Z. Gong, C.-c. Hui, and C. L. Hew (1995)
J. Biol. Chem. 270, 3335-3345
   Abstract »    Full Text »    PDF »
A role for En-2 and other murine homologues of Drosophila segment polarity genes in regulating positional information in the developing cerebellum.
K. Millen, C. Hui, and A. Joyner (1995)
Development 121, 3935-3945
   Abstract »    PDF »
The mouse homolog of the orphan nuclear receptor tailless is expressed in the developing forebrain.
A. Monaghan, E Grau, D Bock, and G Schutz (1995)
Development 121, 839-853
   Abstract »    PDF »
Mitotic delay dependent survival identifies components of cell cycle control in the Drosophila blastoderm.
D. Ruden and H Jackle (1995)
Development 121, 63-73
   Abstract »    PDF »
Developmental evolution: insights from studies of insect segmentation.
N. Patel (1994)
Science 266, 581-590
   Abstract »    PDF »
Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum.
W Wurst, A. Auerbach, and A. Joyner (1994)
Development 120, 2065-2075
   Abstract »    PDF »
Maintenance of Wnt-3 expression in Purkinje cells of the mouse cerebellum depends on interactions with granule cells.
P. Salinas, C Fletcher, N. Copeland, N. Jenkins, and R Nusse (1994)
Development 120, 1277-1286
   Abstract »    PDF »
Abnormal embryonic cerebellar development and patterning of postnatal foliation in two mouse Engrailed-2 mutants.
K. Millen, W Wurst, K Herrup, and A. Joyner (1994)
Development 120, 695-706
   Abstract »    PDF »
Two enhancer regions in the mouse En-2 locus direct expression to the mid/hindbrain region and mandibular myoblasts.
C Logan, W. Khoo, D Cado, and A. Joyner (1993)
Development 117, 905-916
   Abstract »    PDF »
Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos.
A. F. Candia, J. Hu, J. Crosby, P. A. Lalley, D. Noden, J. H. Nadeau, and C. V. Wright (1992)
Development 116, 1123-1136
   Abstract »    PDF »
Embryonic lethality in mice homozygous for a targeted disruption of the N-myc gene..
J Charron, B A Malynn, P Fisher, V Stewart, L Jeannotte, S P Goff, E J Robertson, and F W Alt (1992)
Genes & Dev. 6, 2248-2257
   Abstract »    PDF »
Synergistic principles of development: overlapping patterning systems in Xenopus mesoderm induction.
D. Kimelman, J. L. Christian, and R. T. Moon (1992)
Development 116, 1-9
   Abstract »    PDF »
Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests an important role in early postimplantation mouse development.
F. Del Amo, D. Smith, P. Swiatek, M Gendron-Maguire, R. Greenspan, A. McMahon, and T Gridley (1992)
Development 115, 737-744
   Abstract »    PDF »
The Role of Retinoids in Normal and Abnormal Embryonic Craniofacial Morphogenesis.
J. M. Richman (1992)
Critical Reviews in Oral Biology & Medicine 4, 93-109
   Abstract »    Full Text »    PDF »
Of fin and fur: mutational analysis of vertebrate embryonic development..
J Rossant and N Hopkins (1992)
Genes & Dev. 6, 1-13
   PDF »
Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice..
G Friedrich and P Soriano (1991)
Genes & Dev. 5, 1513-1523
   Abstract »    PDF »
Decoupled evolution of coding region and mRNA expression patterns after gene duplication: Implications for the neutralist-selectionist debate.
A. Wagner (2000)
PNAS 97, 6579-6584
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)