Abstract
The murine genome contains at least 30 sequences related to the Drosophila Antennapedia homeobox. The so-called Hox genes are clustered in four complexes conserved throughout vertebrate evolution1–5, and accumulating evidence shows that these genes are expressed during ontogenesis in a coordinated manner3,6–8 and may be involved in a regulatory network controlling vertebrate morphogenesis. Retinoic acid (RA) or related retinoid derivatives are candidates for crucial signalling molecules involved in vertebrate morphogenetic processes and/or pattern formation as best exemplified by the developing and regenerating limb system (reviewed in refs. 9,10). RA can interfere very specifically with anteroposterior (A-P) patterning in the chick wing bud 11 and is believed to be a natural morphogen released as a concentration gradient from a discrete posterior area, the zone of polarizing activity (ZPA)12. RA can also disturb positional information in the regenerating amphibian limb13,14 The molecular basis of RA activity involves its binding to a cellular RA binding protein (CRABP) 15 and/or to an appropriate nuclear RA receptors (RARs). An increasing number of such RA receptors are being characterized and all of them are ligand-inducible transcription factors belonging to the steroid hormones receptors family16–19. There is increasing evidence that in cultured cells, RA regulates the steady state level of Hox genes messenger RNAs though the transcriptional or post-transcriptional nature of this regulation is not yet clearly established (see e.g. ref.20). In addition, the human Hox-2 genes respond to RA treatment, in teratocarcinoma cell lines, in a way related to their respective positions within the Hox-2 complex21. The molecular mechanism involved in such a colinear response is not known but probably parallels those regulating the expression of these genes during ontogenesis. Using the vertebrate limb development as a model system, we would like to discuss here some circumstantial evidence that RA, RARs and Hox genes may also be functionally related in vivo, in the light of recent findings concerning the expression of such genes during mouse development.
Copyright for this chapter is retained by the author.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
A. M. Colberg-Poley, S. D. Voss, K. Chowdhury, C. L. Stewart, E. F. Wagner, and P. Gruss, Clustered homeo boxes are differentially expressed during murine development,Cell 43:39 (1987).
C. P. Hart, A. Fainsod, and F. H. Ruddle, Sequence analysis of the murine Hox2.2, -2.3, and -2.4 homeo-boxes: evolutionary and structural comparisons, Genomics 1:182 (1989).
D. Duboule and P. Dollé, The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes, EMBO J. 8:1497 (1989).
K. Schughart, C. Kappen, and F. H. Ruddle, Mammalian homeobox-containing genes: Genome organization, structure, expression and evolution, Br. J. Cancer 58:9 (1988).
K. Schughart, C. Kappen and F. H. Ruddle, Duplication of large genomic regions during the evolution of vertebrate homeobox genes, Proc. Natl. Acad. Sci. USA 86:7067 (1989).
S. J. Gaunt, P.T. Sharpe and D. Duboule, Spatially restricted domains of homeogene transcripts in mouse embryos: relation to a segmented body plan, Development 104:71 (1988).
A. Graham, N. Papalopulu, J. Lorimer, J. -H. McVey, E. G. J. Tuddenham and R. Krumlauf, The murine and drosophila homeobox gene complexes have common features of organization and expression, Cell 57:367 (1989).
M. Akam, Hox and HOM, homologous gene clusters in insects and vertebrates, Cell 57:347 (1989).
J. P. Brockes, Retinoids, homeobox genes and limb morphogenesis, Neuron 2:1285 (1989).
G. Eichele, Retinoids and vertebrate limb pattern formation, TIG 5:246 (1989).
C. Tickle, B. Alberts, L. Wolpert, and J. Lee, Local application of retinoic acid to the limb bud mimics the action of the polarizing region, Nature 296:564 (1982).
C. Thaller, and G. Eichele, Identification and spatial distribution of retinoids in the developing chick limb bud, Nature 327: 625 (1987).
M. Maden, Vitamin A and pattern formation in the regenerating limb, Nature 295:672 (1982).
S. D. Thorns, and D. L. Stocum, Retinoic acid-induced pattern duplication in regenerating urodele limbs, Dev.Biol. 103:319 (1984).
D. E. Ong, and G. Chytil, Cellular retinoic acid-binding protein from rat testis, J. Biol.Chem. 253:4551 (1978b).
M. Pektovich, N. J. Brand, A. Krust and P. Chambon, A retinoic acid receptor which belongs to the family of nuclear receptors, Nature 330, 444–450 (1987).
V. Giguère, S. E.Ong, P. Segui, and R. M. Evans, Identification of a receptor for the morphogen retinoic acid, Nature 330:624 (1987).
A. Zelent, A. Krust, M. Pektovich, P.Kastner, and P.Chambon, Cloning of murine a and b retinoic acid receptors and a novel receptor g predominantly expressed in skin, Nature 339:714 (1989).
R.M.Evans, The steroid and thyroid hormone receptor superfamily,Science240:889(1988)
F. Mavilio, A. Simeone, E. Boncinelli, P.W. Andrews, Activation of four homeobox gene clusters in human embryonal carcinoma cells induced to differentiate by retinoic acid, Differentiation 37:73 (1988).
A. Simeone, D. Acamora, L. Arcioni, P. W. Andrews, E. Boncinelli, and F. Mavilio, Human Hox2 Homeobox genes are sequentially activated by retinoic acid in embryonal carcinoma cells, Nature In Press (1990).
P. Dollé, J.-C. Izpisuá-Belmonte, H. Falkenstein, A. Renucci, and D. Duboule, Coordinate expression of the murine Hox-5 complex homeobox-containing genes during limb pattern formation, Nature,342:767 (1989).
G. Oliver, N. Sidell, W. Fiske, C. Heinjmann, T. Mohandas, R. S. Sparkes, and E. M. DeRobertis, Complementary homeoprotein gradients in developing limb buds, Genes and Dev., 3:641 (1989).
C. Tickle, G.Shilswell, A. Crawley, and L. Wolpert, Positional signalling by mouse limb polarizing region in the chick wing bud, Nature 259:396 (1976).
C. Thaller, and G. Eichele, Isolation of 3,4-didehydroretinoic acid, a novel morphogenetic signal in the chick wing bud, Nature 345:815 (1990)
P. Dollé, E. Ruberte, P.Kastner, M. Petkovich, C. M. Stoner, L.Gudas, and P. Chambon, Differential expression of genes encoding a, b and g retinoic acid receptors and CRABP in the developing limbs of the mouse, Nature 342:702 (1989).
P. Dolle, E. Ruberte, P. Leroy, G. M. Morris-Kay, and P.Chambon, Retinoic acid receptors and cellular retinoid binding proteins I: a systematic study of their differential pattern of transcription during mouse organogenesis. Development In Press (1990).
E. Ruberte, P. Dollé, A.Crust, A. Zelent, G. Morriss-Kay, and P. Chambon, Specific spatial and temporal distribution of retinoic acid receptor gamma transcripts during mouse embryogenesis, Development 108:213 (1990).
M. Maden, and D. Summerbell, Retinoic acid-binding protein in the chick limb bud: identification at developmental stages and binding affinities of various retinoids, J. Embryol. exp. Morph. 97: 239 (1986).
D. Summerbell, J. H. Lewis, and L. Wolpert, Positional information in chick limb morphogenesis, Nature 244:492 (1973).
M. Maden, D. E. Ong, D. Summerbell, and F. Chytil, Spatial distribution of cellular protein-binding to retinoic acid in the chick limb bud, Nature 335:733 (1988).
H. Ide, and H. Aono, Retinoic acid promotes proliferation and chondrogenesis in the distal mesodermal cells of chick limb bud, Developmental Biol. 130:767 (1988).
D. F. Paulsen, R. M.Langille, V. Dress, and M. Solursh, Selective stimulation of in vitro limb-bud chondrogenesis by retinoic acid, Differentiation 39:123 (1988).
C. Tickle, and A. Crawley, The effect of local application of retinoids to different positions along the proximo-distal axis of embryonic chick wings, Roux’Árch.Dev.Biol. 197:27 (1988).
D. M. Kochhar, J. D. Penner, and C. Tellone, Comparative teratogenic activities of two retinoids: Effects on palate and limb development. Teratg. Carcinog. Mutagen. 4:377 (1984).
E. B. Lewis, A gene complex controlling segmentation in Drosophila, Nature 276: 556 (1978).
S. J. Gaunt, Homeo-box gene Hox-1.5 expression in mouse embryos: earliest detection by in situ hybridization is during gastrulation, Development 101:51 (1987).
A. J. Durston, J. P. M. Timmermans, W. J. Hage, H. F. J. Hendriks, N. J. De Vires, M. Heideveld, and P. D.Nieuwkoop, Retinoic acid causes an anteposterior transformation in the developing central nervous system, Nature 340:140 (1989).
A. Hornbuch, and L. Wolpert, L., Positional signalling by Hensen’s node when grafted to the chick limb bud, J. Embryol. exp. Morph 94:257 (1986).
M. Wagner, C. Thaller, T. Jessell, and G. Eichele, Polarizing activity and retinoid synthesis in the floor plate of the neural tube, Nature, 345:819 (1990).
S. J. Gaunt, P. L. Coletta, D. Pravtcheva, and P. T. Sharpe, Mouse Hox-3.4: homeobox sequence and embryonic expression patterns compared with other members of the Hox gene network, Development 109:329 (1990).
D. G. Wilkinson, S. Bhatt, M. Cook, E. Boncinelli, and R. Krumlauf, Segmental expression of Hox-2 homeobox-containing genes in the developing mouse hindbrain, Nature 341:405 (1989).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer Science+Business Media New York
About this chapter
Cite this chapter
Dollé, P., Ruberte, E., Izpisùa-Belmonte, JC., Falkenstein, H., Chambon, P., Duboule, D. (1991). A Comparison of the Expression Domains of the Murine Hox-4, RARs and CRABP Genes Suggests Possible Functional Relationships During Patterning of the Vertebrate Limb. In: Hinchliffe, J.R., Hurle, J.M., Summerbell, D. (eds) Developmental Patterning of the Vertebrate Limb. NATO ASI Series, vol 205. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3310-8_11
Download citation
DOI: https://doi.org/10.1007/978-1-4615-3310-8_11
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6457-3
Online ISBN: 978-1-4615-3310-8
eBook Packages: Springer Book Archive