Summary
The palatal cleft seen in Msx-1 knock-out mice suggests a role for this gene in normal palate development. The cleft is presumed secondary to tooth and jaw malformations, since in situ hybridization suggests that Msx-1 mRNA is not highly expressed in developing palatal tissue. In this study we demonstrate, by Northern blot analysis, the expression of Msx-1, but not Msx-2, in the developing palate and in primary cultures of murine embryonic palate mesenchymal cells. Furthermore, we propose a role for Msx-1 in retinoic acid-induced cleft palate, since retinoic acid inhibits Msx-1 mRNA expression in palate mesenchymal cells. We also demonstrate that transforming growth factor beta inhibits Msx-1 mRNA expression in palate mesenchymal cells, with retinoic acid and transforming growth factor beta acting synergistically when added simultaneously to these cells. These data suggest a mechanistic interaction between retinoic acid, transforming growth factor beta, and Msx-1 in the etiology of retinoic acid-induced cleft palate.
Similar content being viewed by others
References
Abbott, B.; Pratt, R. Influence of retinoids and EGF on growth of embryonic mouse palatal epithelia in culture. In Vitro Cell. Dev. Biol. 24:343–352; 1988.
Barlow, A. J.; Francis-West, P. H. Ectopic application of recombinant BMP-2 and BMP-4 can change patterning of developing chick facial primordia. Development 124:391–398; 1997.
Bell, J. R.; Noveen, A.; Liu, Y. H., et al. Genomic structure, chromosomal location, and evolution of the mouse Hox 8 gene. Genomics 16:123–131; 1993.
Brandon, E. P.; Idzerda, R. L.; McKnight, G. S. Targeting the mouse genome: a compendium of knockouts. Curr. Biol. 5:1–27; 1995.
Brown, J. M.; Robertson, K. E.; Wedden, S. E., et al. Alterations in Msx 1 and Msx 2 expression correlate with inhibition of outgrowth of chick facial primordia induced by retinoic acid. Anat. Embryol. 195:203–207; 1997.
Chomczynski, P.; Saachi, N. Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156–159; 1987.
Coelho, C. N. D.; Upholt, W. B.; Kosher, R. A. The expression pattern of the chicken homeobox-containing gene GHox-7 in developing polydactylous limb buds suggests its involvement in apical ectodermal ridge-directed outgrowth of limb mesoderm and in programmed cell death. Differentiation 52:129–137; 1993.
Davidson, D. The function and evolution of Msx genes: pointers and paradoxes. Trends Genet. 11:405–411; 1995.
Davidson, D.; Hill, R. E. Msh-like genes: a family of homeobox genes with wide-ranging expression during vertebrate development. Sem. Dev. Biol. 2:405–412; 1991.
Dolle, P.; Fraulob, V.; Kastner, P., et al. Developmental expression of murine retinoid X receptor (RXR) genes. Mech. Dev. 45:91–104; 1994.
Dolle, P.; Ruberte, E.; Kastner, P., et al. Differential expression of genes encoding α, β and γ retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature 342:702–705; 1989.
Ferguson, M. W. J. Craniofacial malformations: towards a molecular understanding. Nature Genet. 6:329–330; 1995.
Fitzpatrick, D.; Abbott, B; Akhurst, R. Palatal expression of TGF-B isoforms and retinoic acid-treated mouse embryos In: Morris-Kay, G., ed. Retinoids in normal development and teratogenesis. Oxford: Oxford University Press; 1992:149–164.
Foerst-Potts, L.; Sadler, T. W. Disruption of Msx-1 and Msx-2 reveals roles for these genes in craniofacial, eye, and axial development. Dev. Dyn. 209:70–84; 1997.
Hill, R. E.; Jones, P. F.; Rees, A. R., et al. A new family of homeo box-containing genes: molecular structure, chromosomal location, and developmental expression of Hox-7.1. Genes Dev. 3:26–37; 1989.
Hofmann, C.; Eichele, G. Retinoids in development. In: Sporn, M. B.; Roberts, A. B.; Goodman, D. S., ed. The retinoids. New York: Raven Press, Ltd.; 1994:387–442.
Jowett, A. K.; Vainio, S.; Ferguson, M. W. J., et al. Epithelial-mesenchymal interactions are required for msx 1 and msx 2 gene expression in the developing murine tooth. Development 117:461–470; 1993.
Kerr, L.; Miller, D.; Martrisian, L. TGF-β1 inhibition of transin/stromelysin gene expression is mediated through a fos binding sequence. Cell 6:267–278; 1990.
Kochhar, D.; Johnson, E. J. Morphological and autoradiographic studies of cleft palate induced embryos by maternal hypervitaminosis A. Embryol. Exp. Morphol. 14:223–238; 1965.
Kuzoka, M.; Takahashi, T.; Guron, C., et al. Murine homeobox- containing gene, MSX-1: analysis of genomic organization, promoter structure, and potential autoregulatory cis-acting elements. Genomics 21:85–94; 1994.
Lammer, E. J.; Chen, D. T.; Hoar, R. M., et al. Retinoic acid embryopathy. N. Engl. J. Med. 313:837–841; 1985.
Leid, M.; Kastner, P.; Durand, B., et al. Retinoic acid signal transduction pathways. Ann. NY Acad. Sci. 684:19–34; 1993.
Lohnes, D.; Mark, M.; Mendelsohn, C., et al. Developmental roles of the retinoic acid receptors. J. Steroid Biochem. Mol. Biol. 53:475–486; 1995.
Lyons, G. E.; Houzelstein, D.; Sassoon, D., et al. Multiple sites of Hox-7 expression during mouse embryogenesis: comparison with retinoic acid receptor mRNA localization. Mol. Reprod. Dev. 32:303–314; 1992.
Mackenzie, A.; Ferguson, M. W. J.; Sharpe, P. T. Hox-7 expression during murine craniofacial development. Development 113:601–611; 1991.
Mackenzie, A.; Ferguson, M. W.; Sharpe, P. T. Expression patterns of the homeobox gene, hox-8, in the mouse embryo suggest a role in specifying tooth initiation and shape. Development 115:403–420; 1992.
Mackenzie, A.; Leeming, G. L.; Jowett, A. K., et al. The homeobox gene hox 7.1 has specific regional and temporal expression patterns during early murine craniofacial embryogenesis, especially tooth development in vivo and in vitro. Development 111:269–285; 1991.
Mangelsdorf, D.; Kliewer, S.; Kakizuka, A., et al. Retinoid receptors. Recent Prog. Horm. Res. 48:99–121; 1993.
Mina, M.; Gluhak, J.; Upholt, W. B., et al. Experimental analysis of msx-1 and msx-2 gene expression during chick mandibular morphogenesis. Dev. Dyn. 202:195–214; 1995.
Morriss-Kay, G. Retinoic acid and development. Pathobiology 60:264–270; 1992.
Nugent, P.; Greene, R. M. Interactions between the transforming growth factor beta (TGF-β) and retinoic acid signal transduction pathways in murine embryonic palatal cells. Differentiation 58:149–155; 1994.
Nugent, P.; Potchinsky, M.; Lafferty, C., et al. TGF-β modulates the expression of retinoic acid-induced RAR-β in primary cultures of embryonic palate cells. Exp. Cell Res. 220:495–500; 1995.
Rifas, L.; Towler, D. A.; Avioli, L. V. Gestational exposure to ethanol suppresses msx2 expression in developing mouse embryos. Proc. Natl. Acad. Sci. 94:7549–7554; 1997.
Robert, B.; Sassoon, D.; Jacq, B., et al. Hox-7, a mouse homeobox gene with a novel pattern of expression during embryogenesis. EMBO J. 8:91–100; 1989.
Roberts, A. B.; Flanders, K. C.; Kondaiah, P., et al. Transforming growth factor β: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Prog. Horm. Res. 44:157–195; 1988.
Rothman, K. J.; Moore, L. L.; Singer, M., et al. Teratogenicity of high vitamin A intake. N. Engl. J. Med. 333:1369–1415; 1995.
Satokata, I.; Maas, R. Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development. Nat. Genet. 6:348–356; 1994.
Tabin, C. The initiation of the limb bud: growth factors, hox genes, and retinoids. Cell 80:671–674; 1995.
Turecková, J.; Sahlberg, C.; Åberg, T., et al. Comparison of expression of the msx-1, msx-2, BMP-2 and BMP-4 genes in the mouse upper diastemal and molar tooth primordia. Int. J. Dev. Biol. 39:459–468; 1995.
Wang, Y.; Sasson, D. Ectoderm-mesenchyme and mesenchyme-mesenchyme interactions regulate Msx-1 expression and cellular differentiation in the murine limb bud. Dev. Biol. 168:374–382; 1995.
Whiting, J. Craniofacial abnormalities induced by the ectopic expression of homeobox genes. Mutat. Res. 396:97–112; 1997.
Yokouchi, Y.; Oshugi, K.; Sasaki, H., et al. Chicken homeobox gene Msx-1: structure, expression in limb buds and effect of retinoic acid. Development 113:431–444; 1991.
Yoshikawa, H.; Kukita, T.; Kurisu, K., et al. Effect of retinoic acid on in vitro proliferation activity and glycosaminoglycan synthesis of mesenchymal cells from palatal shelves of mouse fetuses. J. Craniofac. Gen. Dev. Biol. 7:45–51; 1987.
Zelent, A.; Krust, A.; Petkovich, M., et al. Cloning of murine α and β retinoic acid receptors and a novel receptor γ predominantly expressed in skin. Nature 339:714–717; 1989.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nugent, P., Greene, R.M. Msx-1 gene expression and regulation in embryonic palatal tissue. In Vitro Cell.Dev.Biol.-Animal 34, 831–835 (1998). https://doi.org/10.1007/s11626-998-0038-5
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11626-998-0038-5