|
|
|
Research Papers
Laboratory of Eukaryotic Molecular Genetics, Medical Research Council National Institute for Medical Research, London, England.
Abstract
Murine Hox genes are organized into four clusters that share many features with the homeotic clusters of Drosophila. This evolutionary conservation and the clear relationships between the position of a gene within a cluster and its expression pattern have led to the suggestion that the structure of the cluster is essential for proper regulation. Using a Hox-2.6-lacZ reporter gene in transgenic mice we have shown that the overall expression pattern of the endogenous Hox-2.6 gene can be reconstructed when it is isolated from the complex. The transgene was expressed in the proper tissues, with the correct spatial distribution and temporal pattern. Furthermore, direct comparison by in situ hybridization revealed that the levels of transgene expression are similar to those of the endogenous gene. This has allowed us to define three elements that regulate particular aspects of the Hox-2.6 pattern, two of which act as spatially specific enhancers. One enhancer, region A, directed expression only in the neural tube, whereas the other, region C, specified the majority of the Hox-2.6 pattern. Both were also capable of imposing the correct boundaries of expression on heterologous promoters. The definition of such elements will allow the characterization of the trans-acting factors that mediate spatial regulation in the mammalian embryo.
This article has been cited by other articles:
![]() |
A. Abzhanov, S. J. Rodda, A. P. McMahon, and C. J. Tabin Regulation of skeletogenic differentiation in cranial dermal bone Development, September 1, 2007; 134(17): 3133 - 3144. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. L. Allen, T. Tenzen, and A. P. McMahon The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development Genes & Dev., May 15, 2007; 21(10): 1244 - 1257. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Mao, J. Barrow, J. McMahon, J. Vaughan, and A. P. McMahon An ES cell system for rapid, spatial and temporal analysis of gene function in vitro and in vivo Nucleic Acids Res., October 12, 2005; 33(18): e155 - e155. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Ferretti, F. Cambronero, S. Tumpel, E. Longobardi, L. M. Wiedemann, F. Blasi, and R. Krumlauf Hoxb1 Enhancer and Control of Rhombomere 4 Expression: Complex Interplay between PREP1-PBX1-HOXB1 Binding Sites Mol. Cell. Biol., October 1, 2005; 25(19): 8541 - 8552. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-M. I. Yu, B. Jerchow, T.-J. Sheu, B. Liu, F. Costantini, J. E. Puzas, W. Birchmeier, and W. Hsu The role of Axin2 in calvarial morphogenesis and craniosynostosis Development, April 15, 2005; 132(8): 1995 - 2005. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. P. Stemmler, A. Hecht, and R. Kemler E-cadherin intron 2 contains cis-regulatory elements essential for gene expression Development, March 1, 2005; 132(5): 965 - 976. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Jeong and A. P. McMahon Growth and pattern of the mammalian neural tube are governed by partially overlapping feedback activities of the hedgehog antagonists patched 1 and Hhip1 Development, January 1, 2005; 132(1): 143 - 154. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. C. M. Brun, J. M. Bjornsson, M. Magnusson, N. Larsson, P. Leveen, M. Ehinger, E. Nilsson, and S. Karlsson Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells Blood, June 1, 2004; 103(11): 4126 - 4133. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Jeong, J. Mao, T. Tenzen, A. H. Kottmann, and A. P. McMahon Hedgehog signaling in the neural crest cells regulates the patterning and growth of facial primordia Genes & Dev., April 15, 2004; 18(8): 937 - 951. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Brend, J. Gilthorpe, D. Summerbell, and P. W. J. Rigby Multiple levels of transcriptional and post-transcriptional regulation are required to define the domain of Hoxb4 expression Development, June 15, 2003; 130(12): 2717 - 2728. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. L. Ligon, Y. Echelard, S. Assimacopoulos, P. S. Danielian, S. Kaing, E. A. Grove, A. P. McMahon, and D. H. Rowitch Loss of Emx2 function leads to ectopic expression of Wnt1 in the developing telencephalon and cortical dysplasia Development, May 15, 2003; 130(10): 2275 - 2287. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Bel-Vialar, N. Itasaki, and R. Krumlauf Initiating Hox gene expression: in the early chick neural tube differential sensitivity to FGF and RA signaling subdivides the HoxB genes in two distinct groups Development, March 13, 2003; 129(22): 5103 - 5115. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Gilthorpe, M. Vandromme, T. Brend, A. Gutman, D. Summerbell, N. Totty, and P. W. J. Rigby Spatially specific expression of Hoxb4 is dependent on the ubiquitous transcription factor NFY Development, March 10, 2003; 129(16): 3887 - 3899. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. G. L. Koh, K. Lam, A. Christoffels, M. V. Erdmann, S. Brenner, and B. Venkatesh Hox gene clusters in the Indonesian coelacanth, Latimeriamenadoensis PNAS, February 4, 2003; 100(3): 1084 - 1088. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. R. Barrow, K. R. Thomas, O. Boussadia-Zahui, R. Moore, R. Kemler, M. R. Capecchi, and A. P. McMahon Ectodermal Wnt3/beta -catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge Genes & Dev., February 1, 2003; 17(3): 394 - 409. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Long, X. M. Zhang, S. Karp, Y. Yang, and A. P. McMahon Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation Development, December 15, 2001; 128(24): 5099 - 5108. [Abstract] [Full Text] [PDF] |
||||
![]() |
W.-F. Shen, K. Krishnan, H. J. Lawrence, and C. Largman The HOX Homeodomain Proteins Block CBP Histone Acetyltransferase Activity Mol. Cell. Biol., November 1, 2001; 21(21): 7509 - 7522. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Manzanares, S. Bel-Vialar, L. Ariza-McNaughton, E. Ferretti, H. Marshall, M. M. Maconochie, F. Blasi, and R. Krumlauf Independent regulation of initiation and maintenance phases of Hoxa3 expression in the vertebrate hindbrain involve auto- and cross-regulatory mechanisms Development, September 15, 2001; 128(18): 3595 - 3607. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. M. Giannola, W. D. Shlomchik, M. Jegathesan, D. Liebowitz, C. S. Abrams, T. Kadesch, A. Dancis, and S. G. Emerson Hematopoietic Expression of HOXB4 Is Regulated in Normal and Leukemic Stem Cells through Transcriptional Activation of the HOXB4 Promoter by Upstream Stimulating Factor (USF)-1 and USF-2 J. Exp. Med., November 20, 2000; 192(10): 1479 - 1490. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Wallace, R. Ansell, J. Clark, and J. McWhir Pre-selection of integration sites imparts repeatable transgene expression Nucleic Acids Res., March 15, 2000; 28(6): 1455 - 1464. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Kmita, F. van der Hoeven, J. Zákány, R. Krumlauf, and D. Duboule Mechanisms of Hox gene colinearity: transposition of the anterior Hoxb1 gene into the posterior HoxD complex Genes & Dev., January 15, 2000; 14(2): 198 - 211. [Abstract] [Full Text] |
||||
![]() |
H. Dassule, P Lewis, M Bei, R Maas, and A. McMahon Sonic hedgehog regulates growth and morphogenesis of the tooth Development, January 11, 2000; 127(22): 4775 - 4785. [Abstract] [PDF] |
||||
![]() |
D Summerbell, P. Ashby, O Coutelle, D Cox, S Yee, and P. Rigby The expression of Myf5 in the developing mouse embryo is controlled by discrete and dispersed enhancers specific for particular populations of skeletal muscle precursors Development, January 9, 2000; 127(17): 3745 - 3757. [Abstract] [PDF] |
||||
![]() |
S Naylor, M. Smalley, D Robertson, B. Gusterson, P. Edwards, and T. Dale Retroviral expression of Wnt-1 and Wnt-7b produces different effects in mouse mammary epithelium J. Cell Sci., January 6, 2000; 113(12): 2129 - 2138. [Abstract] [PDF] |
||||
![]() |
E Ferretti, H Marshall, H Popperl, M Maconochie, R Krumlauf, and F Blasi Segmental expression of Hoxb2 in r4 requires two separate sites that integrate cooperative interactions between Prep1, Pbx and Hox proteins Development, January 1, 2000; 127(1): 155 - 166. [Abstract] [PDF] |
||||
![]() |
T. P. Yamaguchi, S. Takada, Y. Yoshikawa, N. Wu, and A. P. McMahon T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification Genes & Dev., December 15, 1999; 13(24): 3185 - 3190. [Abstract] [Full Text] |
||||
![]() |
D. H. Rowitch, B. St.-Jacques, S. M. K. Lee, J. D. Flax, E. Y. Snyder, and A. P. McMahon Sonic hedgehog Regulates Proliferation and Inhibits Differentiation of CNS Precursor Cells J. Neurosci., October 15, 1999; 19(20): 8954 - 8965. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Lakshmanan, K. H. Lieuw, K.-C. Lim, Y. Gu, F. Grosveld, J. D. Engel, and A. Karis Localization of Distant Urogenital System-, Central Nervous System-, and Endocardium-Specific Transcriptional Regulatory Elements in the GATA-3 Locus Mol. Cell. Biol., February 1, 1999; 19(2): 1558 - 1568. [Abstract] [Full Text] [PDF] |
||||
![]() |
A Locascio, F Aniello, A Amoroso, M Manzanares, R Krumlauf, and M Branno Patterning the ascidian nervous system: structure, expression and transgenic analysis of the CiHox3 gene Development, January 11, 1999; 126(21): 4737 - 4748. [Abstract] [PDF] |
||||
![]() |
M Maconochie, R Krishnamurthy, S Nonchev, P Meier, M Manzanares, P. Mitchell, and R Krumlauf Regulation of Hoxa2 in cranial neural crest cells involves members of the AP-2 family Development, January 4, 1999; 126(7): 1483 - 1494. [Abstract] [PDF] |
||||
![]() |
T. Yamaguchi, A Bradley, A. McMahon, and S Jones A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo Development, January 3, 1999; 126(6): 1211 - 1223. [Abstract] [PDF] |
||||
![]() |
M Manzanares, S Cordes, L Ariza-McNaughton, V Sadl, K Maruthainar, G Barsh, and R Krumlauf Conserved and distinct roles of kreisler in regulation of the paralogous Hoxa3 and Hoxb3 genes Development, January 2, 1999; 126(4): 759 - 769. [Abstract] [PDF] |
||||
![]() |
D. Rowitch, Y Echelard, P. Danielian, K Gellner, S Brenner, and A. McMahon Identification of an evolutionarily conserved 110 base-pair cis-acting regulatory sequence that governs Wnt-1 expression in the murine neural plate Development, January 7, 1998; 125(14): 2735 - 2746. [Abstract] [PDF] |
||||
![]() |
A. Packer, D. Crotty, V. Elwell, and D. Wolgemuth Expression of the murine Hoxa4 gene requires both autoregulation and a conserved retinoic acid response element Development, January 6, 1998; 125(11): 1991 - 1998. [Abstract] [PDF] |
||||
![]() |
M Studer, A Gavalas, H Marshall, L Ariza-McNaughton, F. Rijli, P Chambon, and R Krumlauf Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning Development, January 3, 1998; 125(6): 1025 - 1036. [Abstract] [PDF] |
||||
![]() |
T Theil, M Frain, P Gilardi-Hebenstreit, A Flenniken, P Charnay, and D. Wilkinson Segmental expression of the EphA4 (Sek-1) receptor tyrosine kinase in the hindbrain is under direct transcriptional control of Krox-20 Development, January 2, 1998; 125(3): 443 - 452. [Abstract] [PDF] |
||||
![]() |
C. Liu, K. Shen, Z. Liu, and C. T. Noguchi Regulated Human Erythropoietin Receptor Expression in Mouse Brain J. Biol. Chem., December 19, 1997; 272(51): 32395 - 32400. [Abstract] [Full Text] [PDF] |
||||
![]() |
M K Maconochie, S Nonchev, M Studer, S K Chan, H Popperl, M H Sham, R S Mann, and R Krumlauf Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1. Genes & Dev., July 15, 1997; 11(14): 1885 - 1895. [Abstract] [PDF] |
||||
![]() |
J. McDonough and E. Deneris beta 43': An Enhancer Displaying Neural-Restricted Activity Is Located in the 3'-Untranslated Exon of the Rat Nicotinic Acetylcholine Receptor beta 4 Gene J. Neurosci., April 1, 1997; 17(7): 2273 - 2283. [Abstract] [Full Text] [PDF] |
||||
![]() |
A Gould, A Morrison, G Sproat, R A White, and R Krumlauf Positive cross-regulation and enhancer sharing: two mechanisms for specifying overlapping Hox expression patterns. Genes & Dev., April 1, 1997; 11(7): 900 - 913. [Abstract] [PDF] |
||||
![]() |
H Popperl, C Schmidt, V Wilson, C. Hume, J Dodd, R Krumlauf, and R. Beddington Misexpression of Cwnt8C in the mouse induces an ectopic embryonic axis and causes a truncation of the anterior neuroectoderm Development, January 8, 1997; 124(15): 2997 - 3005. [Abstract] [PDF] |
||||
![]() |
A Morrison, L Ariza-McNaughton, A Gould, M Featherstone, and R Krumlauf HOXD4 and regulation of the group 4 paralog genes Development, January 8, 1997; 124(16): 3135 - 3146. [Abstract] [PDF] |
||||
![]() |
M Tada, M. O'Reilly, and J. Smith Analysis of competence and of Brachyury autoinduction by use of hormone-inducible Xbra Development, January 6, 1997; 124(11): 2225 - 2234. [Abstract] [PDF] |
||||
![]() |
D. E. K. Ferrier and M. Akam Organization of the Hox gene cluster in the grasshopper, Schistocerca gregaria PNAS, November 12, 1996; 93(23): 13024 - 13029. [Abstract] [Full Text] [PDF] |
||||
![]() |
R Ladher, T. Mohun, J. Smith, and A. Snape Xom: a Xenopus homeobox gene that mediates the early effects of BMP-4 Development, January 8, 1996; 122(8): 2385 - 2394. [Abstract] [PDF] |
||||
![]() |
L Zeltser, C Desplan, and N Heintz Hoxb-13: a new Hox gene in a distant region of the HOXB cluster maintains colinearity Development, January 8, 1996; 122(8): 2475 - 2484. [Abstract] [PDF] |
||||
![]() |
P Tremblay, F Pituello, and P Gruss Inhibition of floor plate differentiation by Pax3: evidence from ectopic expression in transgenic mice Development, January 8, 1996; 122(8): 2555 - 2567. [Abstract] [PDF] |
||||
![]() |
A Morrison, M. Moroni, L Ariza-McNaughton, R Krumlauf, and F Mavilio In vitro and transgenic analysis of a human HOXD4 retinoid-responsive enhancer Development, January 6, 1996; 122(6): 1895 - 1907. [Abstract] [PDF] |
||||
![]() |
T Akasaka, M Kanno, R Balling, M. Mieza, M Taniguchi, and H Koseki A role for mel-18, a Polycomb group-related vertebrate gene, during theanteroposterior specification of the axial skeleton Development, January 5, 1996; 122(5): 1513 - 1522. [Abstract] [PDF] |
||||
![]() |
S Nonchev, C Vesque, M Maconochie, T Seitanidou, L Ariza-McNaughton, M Frain, H Marshall, M. Sham, R Krumlauf, and P Charnay Segmental expression of Hoxa-2 in the hindbrain is directly regulated by Krox-20 Development, January 2, 1996; 122(2): 543 - 554. [Abstract] [PDF] |
||||
![]() |
M Frasch, X Chen, and T Lufkin Evolutionary-conserved enhancers direct region-specific expression of the murine Hoxa-1 and Hoxa-2 loci in both mice and Drosophila Development, January 4, 1995; 121(4): 957 - 974. [Abstract] [PDF] |
||||
![]() |
T Knittel, M Kessel, M. Kim, and P Gruss A conserved enhancer of the human and murine Hoxa-7 gene specifies the anterior boundary of expression during embryonal development Development, January 4, 1995; 121(4): 1077 - 1088. [Abstract] [PDF] |
||||
![]() |
M Studer, H Popperl, H Marshall, A Kuroiwa, and R Krumlauf Role of a conserved retinoic acid response element in rhombomere restriction of Hoxb-1 Science, September 16, 1994; 265(5179): 1728 - 1732. [Abstract] [PDF] |
||||
![]() |
K. M. George, M. W. Leonard, M. E. Roth, K. H. Lieuw, D. Kioussis, F. Grosveld, and J. D. Engel Embryonic expression and cloning of the murine GATA-3 gene Development, September 1, 1994; 120(9): 2673 - 2686. [Abstract] [PDF] |
||||
![]() |
M. Dickinson, R Krumlauf, and A. McMahon Evidence for a mitogenic effect of Wnt-1 in the developing mammalian central nervous system Development, January 6, 1994; 120(6): 1453 - 1471. [Abstract] [PDF] |
||||
![]() |
L Jeannotte, M Lemieux, J Charron, F Poirier, and E J Robertson Specification of axial identity in the mouse: role of the Hoxa-5 (Hox1.3) gene. Genes & Dev., November 1, 1993; 7(11): 2085 - 2096. [Abstract] [PDF] |
||||
![]() |
R Vogels, J Charite, W de Graaff, and J Deschamps Proximal cis-acting elements cooperate to set Hoxb-7 (Hox-2.3) expression boundaries in transgenic mice Development, January 5, 1993; 118(1): 71 - 82. [Abstract] [PDF] |
||||
![]() |
S. Ang and J Rossant Anterior mesendoderm induces mouse Engrailed genes in explant cultures Development, January 5, 1993; 118(1): 139 - 149. [Abstract] [PDF] |
||||
![]() |
R. Behringer, D. Crotty, V. Tennyson, R. Brinster, R. Palmiter, and D. Wolgemuth Sequences 5' of the homeobox of the Hox-1.4 gene direct tissue-specific expression of lacZ during mouse development Development, January 3, 1993; 117(3): 823 - 833. [Abstract] [PDF] |
||||