Abstract
Vertebrate Hox genes are required for the proper organization of structures along the rostrocaudal axis. Hoxd-11 is expressed in the posterior part of the embryo, up to the level of prevertebra 27, and its expression boundary is reproduced by a Hoxd-11/lacZ transgene. Expression of this transgene anterior to prevertebra 27 is prevented by the silencing activity of a cis-acting element, region IX. Using transgenic mice, we show that Hoxd-11 repression by region IX is necessary to position the sacrum properly. This silencing activity depends on phylogenetically conserved sequences able to bind in vitro retinoic acid receptors and COUP-TFs. ES cells were used to generate mice carrying a subtle mutation that abolishes binding of nuclear receptors to region IX. Mutant mice display an anterior shift of their lumbosacral transition inherited as a codominant trait. In mutant embryos, expression of both Hoxd-11 and Hoxd-10 mRNAs in the prevertebral column is anteriorized. These results illustrate the sharing, in cis, of a single regulatory element in order to establish the expression boundaries of two neighboring Hoxd genes.
References
33
Referenced
86
10.1126/science.2660260
10.1016/S0021-9258(18)47314-0
/ J. Biol. Chem. / Pure and functionally homogeneous recombinant retinoid X receptor. (1994){'key': '2021111418395333000_10.18.2326.3', 'first-page': '4153', 'article-title': 'Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors. (1992)10.1242/dev.120.8.2187
/ Development / Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of Hoxd-11. (1994)10.1038/375791a0
{'key': '2021111418395333000_10.18.2326.6', 'first-page': '27', 'article-title': 'The in vitro development of blastocyst-derived embryonic stem cell lines: Formation of visceral yolk sac, blood islands and myocardium.', 'volume': '87', 'year': '1985', 'journal-title': 'J. Embryol. Exp. Morpholol.'}
/ J. Embryol. Exp. Morpholol. / The in vitro development of blastocyst-derived embryonic stem cell lines: Formation of visceral yolk sac, blood islands and myocardium. (1985)-
Dollé, P., Dierich, A. Le Meur M. Schimmang, T. Schuhbaur, B. Chambon, P. and Duboule. D. 1993. Disruption of the Hoxd-13 gene induces localized heterochrony leading to mice with neotenic limbs. Cell 75: 43-1-441.
(
10.1016/0092-8674(93)90378-4
) 10.1016/0925-4773(94)90023-X
10.1073/pnas.92.1.310
10.1242/dev.122.2.449
/ Development / Functional cooperation between the non-paralogous genes Hoxa-10 and Hoxd-11 in the developing forelimb and axial skeleton. (1996)10.1002/j.1460-2075.1993.tb06028.x
/ EMBO J. / Structure and activity of regulatory elements involved in the activation of the Hoxd-11 gene during late gastrulation. (1993)10.1093/nar/16.1.369
10.1016/0092-8674(93)90644-6
10.1002/bies.950140412
{'key': '2021111418395333000_10.18.2326.15', 'first-page': '171', 'article-title': 'Differential staining of cartilage and bone in fetal mouse skeleton by alcian blue and alizarin red.', 'volume': '16', 'year': '1976', 'journal-title': 'Congenital Anom.'}
/ Congenital Anom. / Differential staining of cartilage and bone in fetal mouse skeleton by alcian blue and alizarin red. (1976)10.1002/j.1460-2075.1991.tb07764.x
/ EMBO J. / Murine genes related to the Drosophila AbdB homeotic genes are sequentially expressed during development of the posterior part of the body. (1991)10.1016/0925-4773(94)90098-1
- Joyner, A.L. 1993 Gene targeting. A practical approach. IRL Press at Oxford University Press, Oxford, UK.
10.1016/0092-8674(91)90574-I
10.1016/0092-8674(94)90290-9
10.1126/science.1899293
10.1016/0968-0004(92)90014-Z
10.1242/dev.120.10.2723
/ Development / Function of the retinoic acid receptors (RARs) during development. (I) Craniofacial and skeletal abnormalities in RAR double mutants. (1994)10.1002/j.1460-2075.1993.tb06196.x
/ EMBO J. / The patterns of binding of RAR, RXR and TR homo- and heterodimers to direct repeats are dictated by the binding specificites of the DNA binding domains. (1993)10.1016/0092-8674(95)90200-7
10.1016/S0092-8674(00)81073-9
10.1002/j.1460-2075.1992.tb05190.x
/ EMBO J. / Comparison of mouse and human HOX-4 complexes defines conserved sequences involved in the regulation of Hox-4.4. (1992)10.1242/dev.108.2.213
/ Development / Specific spatial and temporal distribution of retinoic acid receptor gamma transcripts during mouse embryogenesis. (1990)10.1242/dev.111.1.45
/ Development / Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattem of transcription during early morphogenesis in mouse embryos. (1991)10.1101/gad.7.12a.2318
10.1016/S0092-8674(00)81303-3
10.1016/0896-6273(88)90167-5
10.1006/dbio.1996.0137
Dates
Type | When |
---|---|
Created | 18 years, 2 months ago (June 5, 2007, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 14, 2021, 9:52 p.m.) |
Indexed | 1 year, 1 month ago (July 10, 2024, 11:18 a.m.) |
Issued | 28 years, 11 months ago (Sept. 15, 1996) |
Published | 28 years, 11 months ago (Sept. 15, 1996) |
Published Online | 28 years, 11 months ago (Sept. 15, 1996) |
Published Print | 28 years, 11 months ago (Sept. 15, 1996) |
@article{G_rard_1996, title={In vivo targeted mutagenesis of a regulatory element required for positioning the Hoxd-11 and Hoxd-10 expression boundaries.}, volume={10}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.10.18.2326}, DOI={10.1101/gad.10.18.2326}, number={18}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Gérard, M and Chen, J Y and Gronemeyer, H and Chambon, P and Duboule, D and Zákány, J}, year={1996}, month=sep, pages={2326–2334} }