Abstract
9-cis-retinoic acid has recently been found to be a high affinity ligand for the retinoic X receptor (RXR). RXRs are believed to be involved in metabolic activities rather than in morphogenetic ones. Interestingly, RXR has been found to form heterodimers involving other receptors from the steroid family, such as the thyroid hormone receptor, vitamin D receptor or retinoic acid receptors (RARs). In this paper we examined whether or not 9-cis-retinoic acid had any morphogenetic properties on the regenerating axolotl limb. It is shown that 9-cis-retinoic acid proximalized regenerating limbs and was somewhat more potent in this action than all-trans-retinoic acid. Based on these observations, the possible roles of other receptors during pattern formation is discussed.
This is a preview of subscription content, log in via an institution to check access.
References
Blumberg B, Mangelsdorf DJ, Dyck JA, Bittner DA, Evans RM, Robertis EM De (1992) Multiple retinoid-responsive receptors in a single cell: Families of retinoid “X” receptors and retinoic acid receptors in theXenopus egg. Proc Natl Acad Sci USA 89:2321–2325
Brockes JP (1992) Retinoic acid and urodele limb regeneration. Proceedings of the 4th international conference on limb development and regeneration, Asilomar, Calif
Bugge TH, Pohl J, Lonnoy O, Stunnenberg HG (1992) RXRα, a promiscuous partner of retinoic acid and thyroid hormone receptors. EMBO J 11:1409–1418
Dollé P, Ruberte E, Kastner P, Petkovich M, Stoner CM, Gudas LJ, Chambon P (1989) 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
Duboule D (1991) Patterning in the vertebrate limb. Curr Opin Genet Dev 1:211–216
Eichele G (1989) Retinoids and vertebrate limb pattern formation. Trends Genet 5:4–9
Eichele G, Tickle C, Alberts BM (1984) Microcontrolled release of biologically active compounds in chick embryos: Beads of 200-μm diameter for the local release of retinoids. Anal Biochem 142:542–555
Giguère V, Lyn S, Yip P, Siu C-H, Amin S (1990) Molecular cloning of cDNA encoding a second cellular retinoic acid-binding protein. Proc Natl Acad Sci USA 87:6233–6237
Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C (1992) 9-cis-retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 68:397–406
Kim WS, Stocum DL (1986) Retinoic acid modifies positional memory in the anteroposterior axis of regenerating axolotl limbs. Dev Biol 114:170–179
Kliewer SA, Umasono K, Mangelsdorf DJ, Evans RM (1992) Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature 355:446–449
Laudet V, Stehelin D (1992) Flexible friends. Curr Biol 2:293–295
Leid M, Kastner P, Lyons R, Naksharti N, Saunders M, Zacharewski T, Chen J-Y, Staub A, Garnier J-M, Mader S, Chambon P (1992) Purification, cloning and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell 68:377–395
Levin AA, Sturzenbecker LJ, Kazmer S, Bosakowski T, Huselton C, Allenby G, Speck J, Kratzeisen CL, Rosenberg M, Lovey A, Grippo JF (1992) 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRα. Nature 355:359–361
Ludolph DC, Cameron JA, Stocum DL (1990) The effects of retinoic acid on positional memory in the dorsoventral axis of the regenerating axolotl limbs. Dev Biol 140:41–52
Maden M (1982) Vitamin A and pattern formation in the regenerating limb. Nature 295:672–675
Mangelsdorf D, Ong E, Dyck J, Evans M (1990) Nuclear receptor that identifies a novel retinoic acid response pathway. Nature 345:224–229
Mohanty-Hejmadi P, Dutta SK, Mahapatra P (1992) Limbs generated at site of tail amputation in marbled balloon frog after vitamin A treatment. Nature 355:352–353
Morgan BA, Izpisua-Belmonte J-C, Duboule D, Tabin CJ (1992) Targeted misexpression ofHox-4.6 in the avian limb bud causes apparent homeotic transformations. Nature 358:236–239
Oro A, McKeown M, Evans R (1990) Relationship between the product of theDrosophila ultraspiracle locus and the vertebrate retinoid X receptor. Nature 347:298–301
Ragsdale CW Jr, Brockes JP (1991) Retinoids and their targets in vertebrate development. Curr Opin Cell Biol 6:928–934
Ragsdale CW Jr, Petkovich M, Gates PB, Chambon P, Brockes JP (1989) Identification of a novel retinoic acid receptor in regenerative tissues of the newt. Nature 341:654–657
Riley BB, Savage MP, Simandl BK, Olwin BB, Fallon JF (1993) Retroviral expression of FGF-2 (bFGF) affects patterning in chick limb bud. Development 118:95–104
Sherman DR, Lloyd RS, Chytil F (1987) Rat cellular retinol-binding protein: cDNA sequence and rapid retinol-dependent accumulation of mRNA. Proc Natl Acad Sci USA 84:3209–3213
Stocum DL, Maden M (1990) Regenerating limbs. Methods Enzymol 190:189–201
Thaller C, Eichele G (1987) Identification and spacial distribution of retinoids in the developing chick limb bud. Nature 327:625–628
Thaller C, Eichele G (1990) Isolation of 3,4-didehydroretinoic acid, a novel morphogenetic signal in the chick wing bud. Nature 345:815–819
Thaller C, Hofmann C, Eichele G (1993) 9-cis-retinoic acid, a potent inducer of digit pattern duplications in the chick wing bud. Development 118:957–965
Tickle C, Alberts B, Wolpert L, Lee J (1982) Local application of retinoic acid to the limb bud mimics the action of the polarizing region. Nature 296:564–566
Tickle C, Lee J, Eichele G (1985) A quantitative analysis of the effect of all-trans-retinoic acid on the pattern of chick wing development. Dev Biol 109:82–95
Thoms SD, Stocum DL (1984) Retinoic acid-induced pattern duplication in regenerating urodele limbs. Dev Biol 103:319–328
Wanek N, Gardiner DM, Muneoka K, Bryant SV (1991) Conversion by retinoic acid of anterior cells into ZPA cells in the chick wing bud. Nature 350:81–83
Zhang X-K, Lehmann J, Hoffmann B, Dawson MI, Cameron J, Graupner G, Hermann T, Tran T, Pfahl M (1992) Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid. Nature 358:587–591
Author information
Authors and Affiliations
Additional information
Correspondence to: P.A. Tsonis
Rights and permissions
About this article
Cite this article
Tsonis, P.A., Washabaugh, C.H. & Del Rio-Tsonis, K. Morphogenetic effects of 9-cis-retinoic acid on the regenerating limbs of the axolotl. Roux's Arch Dev Biol 203, 230–234 (1994). https://doi.org/10.1007/BF00636339
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00636339