Skip to main content
SpringerLink
Log in

Background to work on retinoids and amphibian limb regeneration: Studies on anuran tadpoles—a retrospect

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

Studies on the effects of exogenous vitamin A palminate on limb development and regeneration in anuran tadpoles carried out since late 1960s at the author’s laboratory are reviewed and discussed. Most significant was the initial discovery that vitamin A causes regeneration of complete or nearly complete limbs instead of only the missing distal part, thus altering the P-D pattern of regeneration—a phenomenon now called proximalization. Often more than one such regenerates develop per stump. Vitamin A produces proximalizing effect on regeneration cells during their dedifferentiation and blastema formation but inhibits regeneration if given once redifferentiation begins. Shank-level blastemas from treated tadpoles grafted into orbits of previously treated/untreated host tadpoles formed complete limbs. Proximalizing effect is proportionate to vitamin A concentration, duration of treatment, amputational level and stage of tadpoles. Vitamin A produces this effect also if given only prior to amputation. Its influence persists after cessation of treatment, declining with time. Proximalizing effect is correlated with natural ability in limbs to regenerate. Vitamin A improves regenerative ability and can induce it to some extent in non-regenerating limbs. Vitamin A excess retards limb development and produces stage dependent teratogenic defects. Further development of only that limb region is prevented in which differentiation is beginning when vitamin A is given. Short treatment of tadpoles beginning with limbs at spatula/paddle stage inhibited foot development in the unoperated limbs hut promoted regeneration of complete limbs from the contra-lateral amputated limbs. These dual effects were due to cells of the former differentiating and of the latter dedifferentiating when exposed to vitamin A palmitate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alam S 1983Studies on the morphogenetic influence of treatment of tadpoles of the anuran Bufo melanostictus Schneider with vitamin A palmitate on limb regeneration, Ph D thesis, University of Rajasthan, Jaipur

    Google Scholar 

  • Alam S and Niazi I A 1980 The pattern of decline and loss of the capacity for hind limb regeneration in the tadpolesof Bufo melanostictus Schneider;Rajasthan Univ. Stud. Zool. 2 105–113

    Google Scholar 

  • Alam S and Niazi I A 1989 The various effects of retinol palmitate on hind limb regeneration inBufo melanostictus tadpoles of different developmental stages, inProceedings of Seventh All India Symposium of Development Biologists (eds) R P Maleyvar and S C God (Kurukshetra: Indian Society of Developmental Biologists) pp 123–132

    Google Scholar 

  • Brockes J P 1989 Retinoids, homeobox genes and limb morphogenesis;Neuron 2 1285–1294

    Article  PubMed  CAS  Google Scholar 

  • Chang C Y, Witschi E and Ponseti I V 1955 Teratogenic effects ofLathyrus odoralus seeds on development and regeneration of vertebrate limbs;Proc. Soc. Exp. Biol. Med. 90 45–50

    PubMed  CAS  Google Scholar 

  • Cohlan S Q 1953 Excessive intake of vitamin A as a cause of congenital anomalies in the rat;Science 117 535–536

    Article  PubMed  CAS  Google Scholar 

  • de Both N J 1970 The developmental potencies of the regeneration blastema of the axolotl;Roux’s Arch. 164 242–276

    Article  Google Scholar 

  • Deck J D and Shapiro S L 1963 Interference with newt limb regeneration by an inhibitor of histamine formation;Anat. Rec. 145 307

    Google Scholar 

  • Drill V A 1943 Interrelationships between thyroid function and vitamin metabolism;Physiol. Rev. 23 355–379

    CAS  Google Scholar 

  • Dinsmore C E 1974 Morphogenetic interactions between minced limb muscle and transplanted blastemas in the axolotl;J. Exp. Zool. 187 223–232

    Article  Google Scholar 

  • Eichele G 1993 Retinoids in embryonic development;Ann. N.Y. Acad. Sci. 678 22–36

    Article  PubMed  CAS  Google Scholar 

  • Faber J 1976 Positional information in the amphibian limb;Acta Biotheor. 25 44–65

    Article  PubMed  CAS  Google Scholar 

  • Fell H B and Rinaldini L M 1965 The effects of vitamin A and C on cells and tissues in culture; inCells and tissues in cultures, methods, biology and physiology (ed.) E N Willmer (New York: Academic Press) vol 1, pp 659–699

    Google Scholar 

  • Gallandre F and Kistler A 1980 Inhibition and reversion of chondrogenesis by retinoic acid in rat limb bud cell cultures;Roux’sArch. Dev. Biol. 189 25–33

    CAS  Google Scholar 

  • Gebhardt DOE and Faber J 1966 The influence of aminoprotein on limb regeneration inAmbystoma mexicanum;J. Embryol. Exp. Morphol. 16 143–158

    PubMed  CAS  Google Scholar 

  • Giroud A and Martinet M 1960 Teratogenic action of hypervitaminosis A in the mouse as a function of the embryonic stage;C. R. Soc. Biol. Paris 154 1353–1355

    PubMed  CAS  Google Scholar 

  • Gupta P 1991Effects of vitamin A on the thyroid glands of anuran larvae, PhD thesis, University of Rajasthan, Jaipur

    Google Scholar 

  • Holtzer H 1959 The development of mesodermal axial structures in regeneration and embryogenesis, inRegeneration in vertebrates (ed.) C S Thornton (Chicago: University of Chicago Press) pp 15–33

    Google Scholar 

  • Ide H 1988 Retinoic acid promotes cell proliferation and cartilage nodule formation in the cultured chick embryo limb buds; inRegeneration and development (eds) S Inoui, T Shirai, M W Egar, S Aiyama, J Geraudie, T Nobunaga and N L Sato (Maebashi: Okada Printing and Publishing Co.) pp 521–529

    Google Scholar 

  • Jangir O P 1979Experimental studies on the ontogenesis of limbs in the anuran Bufo melanostictus (Schneider), PhD thesis, University of Rajasthan, Jaipur

    Google Scholar 

  • Jangir O P and Niazi I A 1977 Increase in developmental potencies of blastemas of regenerating limbs in toad tadpoles exposed to vitamin A excess; 2ndAll India Symposium on Developmental Biology, University of Poona, Pune, Nov. 1977 (Abstract no. 20)

    Google Scholar 

  • Jangir O P and Niazi I A 1978 Stage dependent effects of vitamin A excess on limbs during ontogenesis and regeneration in tadpoles of the toad,Bufo melanostictus Schneider;Indian J. Exp. Biol. 16 438–445

    CAS  Google Scholar 

  • Johnson K J and Scadding R S 1992 The duration of the effectiveness of vitamin A at causing proximo-distal duplication in regenerating limbs of the axolotl,Ambystoma mexicanum, in relation to whole body retinoid levels;J. Exp. Zool. 264 189–195

    Article  CAS  Google Scholar 

  • Kalter H C and Warkany J 1959 Experimental production of congenital malformations in mammals by metabolic procedures;Physiol. Rev. 39 69–115

    PubMed  CAS  Google Scholar 

  • Khan M S 1965 A normal tableof Bufo melanostictus Schneider;Biologica 11 1–39

    Google Scholar 

  • Kim W S and Stocum D L 1986 Effects of retinoids on regenerating limbs: comparison of retinoic acid and arotinoid at different amputation levels;Roux’s Arch. Den. Biol. 195 455–463

    Article  CAS  Google Scholar 

  • Kistler A and Galli B 1979 Retinoic acid induced proteoglycan release and cartilage resorption in rat bone cultures are age dependent and inhibited by EDTA;Roux’s Arch. Den. Biol. 187 59–71

    Article  CAS  Google Scholar 

  • Koussoulakos S 1989 Survey of research work on the regeneration ofTriturus alpestris forelimbs treated with vitamin A palmitate; inRecent trends in regeneratton research (eds) V Kiortsis, S Koussoulakos and H Wallace (New York: Plenum Press) NATO-ASI Series,Series A: Life Sciences 172 355–370

    Google Scholar 

  • Lewis C A, Pratt R M, Pennypacker J P and Hassell J R 1978 Inhibition of limb chondrogenesisin vitro by vitamin A: alteration in cell surface characteristics;Dev. Biol. 64 31–47

    Article  PubMed  CAS  Google Scholar 

  • Lheureux E, Thorns S D and Cary F 1986 The effects of two retinoids inPleurodeles waltz andTrturns vulgaris;J. Embryl. Exp. Morphol. 92 165–182

    CAS  Google Scholar 

  • Ludolph D C, Cameron I A and Stocum D L 1990 The effect of retinoic acid on positional memory in the dorso-ventral axis of regenerating axolotl limbs;Dev. Biol. 140 41–52

    Article  PubMed  CAS  Google Scholar 

  • Maden M 1982 Vitamin A and pattern formation in the regenerating limb;Nature (London) 295 672–675

    Article  CAS  Google Scholar 

  • Maden M 1983 The effects of vitamin A on limb regeneration inRana temporaria;Dev. Biol. 98 409–416

    Article  PubMed  CAS  Google Scholar 

  • Maden M 1989 Commentary on retinoids in regeneration, inRecent trends in regeneration research (eds) V Kiortsis, S Koussoulakos and H Wallace; NATO-ASI series,Series A: Life Sciences 172 371–373

  • Maden M 1993 The homeotic transformation of tails into limbs inRana temporaria by retinoids;Dev. Biol,159 379–391

    Article  PubMed  CAS  Google Scholar 

  • Marin-Padilla M 1966 Mesodermal alterations induced by hypervitaminosis A;J. Embryol. Exp. Morphol. 15 261–264

    PubMed  CAS  Google Scholar 

  • McCarrison R 1923 Pathogenesis of deficiency diseases: No. XI—Observations on fatexcess in relation to iodine requirements to the thyroid glands;Indian J. Med. Res. 11 1–51

    Google Scholar 

  • Mohanty-Hejmadi P, Dutta S K and Mahapatra P 1992 Limbs generated at the site of tail amputation in marbled balloon frog after vitamin A treatment;Nature (London) 355 352–353

    Article  CAS  Google Scholar 

  • Niazi I A 1963 The histology of tail regeneration in the ammocoetes;Can. J. Zool. 41 125–126

    Google Scholar 

  • Niazi I A 1965 Muscle regeneration in frog tadpoles;Zool. Anz. 174 328–337

    Google Scholar 

  • Niazi I A 1966 Role of notochord in regeneration of the tail in frog tadpoles;Acta Anat. 64 341–350

    Article  Google Scholar 

  • Niazi I A 1983 Regeneration studies in India, inDevelopmental biology an Afro-Asian perspective (eds) S C Goel and R Bellairs: (Poona: Indian Society of Developmental Biologists) pp 161–176

    Google Scholar 

  • Niazi I A and Alam S 1984 Regeneration of whole limbs from shank stumps in toad tadpoles treated with vitamin A;Roux’s Arch. Dev. Biol. 193 111–116

    Article  CAS  Google Scholar 

  • Niazi I A, Jangir 0 P, Alam S, Sharma K K and Ratnasamy C 1989 Vitamin A effect on limb regeneration: Studies on the tadpoles of anuran amphibians; inRecent trends in regeneration research (eds) V Kiortsis, S Koussoulakos and H Wallace (New York: Plenum Press); NATO-A SI series,Series A: Life Sciences 172 355 -370

    Google Scholar 

  • Niazi I A, Jangir 0 P and Sharma K K 1979 Forelimb regeneration at wrist level in the adults of skipper frog,Rana cyanophlyctis Schneider and its improvement by vitamin A treatment;Indian J. Exp. Biol. 17 435–437

    PubMed  CAS  Google Scholar 

  • Niazi I A, Pescitelli M J and Stocum D L 1985 Stage dependent effects of retinoic acid on regenerating urodele limbs;Roux’s Arch. Biol. 194 355–363

    Article  CAS  Google Scholar 

  • Niazi I A and Ratnasamy C 1984 Regeneration of whole limbs in toad tadpoles treated with retinol palmitate after the wound healing stage;J. Exp. Zool. 230 501–505

    Article  CAS  Google Scholar 

  • Niazi I A and Saxena S 1968 Inhibitory and modifying influence of excess of vitamin A on tail regeneration inBufo tadpoles;Experientia 24 852–853

    Article  PubMed  CAS  Google Scholar 

  • Niazi I A and Saxena S 1972 The influence of excess vitamin A on the growth of frog tadpoles with particular reference to thyroid glands;Rev. Can. Biol. 31 89–96

    PubMed  CAS  Google Scholar 

  • Niazi I A and Saxena S 1978 Abnormal hind limb regeneration in tadpoles of the toad,Bufo anderosonii exposed to vitamin A excess;Folia Biol. (Krakow) 26 3–8

    CAS  Google Scholar 

  • Niazi I A and Saxena S 1979 Relationship between inhibiting influence of vitamin A and developmental stage of regenerating tail in tadpoles(Bufo andersonii);Indian J. Exp. Biol. 17 866–868

    PubMed  CAS  Google Scholar 

  • Rose S M 1962 Tissue-arch control of regeneration in the amphibian limb; inRegeneration (ed.) D Rudwick (New York: Ronald Press) pp 153–176

    Google Scholar 

  • Saxena S 1973Studies on the influence of vitamin A on development, growth and regeneration in anura (Bufo andersonii Boulanger and Rana cyanophlyctis Schneider), PhD thesis, University of Rajasthan, Jaipur

    Google Scholar 

  • Saxena S and Niazi I A 1977 Effect of vitamin A excess on hind limb regeneration in the tadpoles of the toad,Bufo andersonii Boulanger;Indian J. Exp. Biol. 15 435–439

    PubMed  CAS  Google Scholar 

  • Scadding S R and Maden M 1986 Comparison of the effect of vitamin A on limb development and regenerationinXenopus laevis tadpoles;J. Embryol. Exp. Morphol. 91 35–53

    PubMed  CAS  Google Scholar 

  • Scadding S R and Maden M 1994 Retinoic acid gradients during limb regeneration;Dev. Biol. 162 608–617.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt A J 1968Cellular biology of vertebrate regeneration and repair (Chicago: University of Chicago Press)

    Google Scholar 

  • Sharma K K 1982Investigations on limb regeneration in tadpoles andfroglets of the anuran Rana breviceps Schneider, treated with vitamin A or electrically stimulated, Ph D thesis, University of Rajasthan, Jaipur

    Google Scholar 

  • Sharma K K, Gaur M and Niazi I A 1990–91 Studies on the effect of vitamin A on mitotic activity of blastema cells during hind limb regenerationof Bufo melanostictus tadpoles;J. Zool. Soc. India 42–43 91–98

    Google Scholar 

  • Sharma K K and Niazi I A 1979 Regeneration induced in the forelimbs by treatment with vitamin A in the frogletsof Rana breviceps;Experientia 35 1571–1572

    Article  PubMed  CAS  Google Scholar 

  • Sharma K K and Niazi I A 1983 Effect of vitamin A on metamorphosis in tadpolesof Rana breviceps;Natl. Acad. Sci. Lett. 6 397–399

    CAS  Google Scholar 

  • Sharma K K and Niazi I A 1988 Variety of regenerative responses of different proximo-distal segments of young and advancedRana breviceps tadpoles treated with vitamin A after amputation; inControl of cell proliferation and differentiation during regeneration (ed.) H J Anton (Basel: Kargen)Monogr. Dev Biol. 21 124–137

    Google Scholar 

  • Sharma K K, Niazi I A and Sharma Y 1985 Improvement in morphology of hind limb regenerates ofRana breviceps tadpoles treated with vitamin A palmitate after amputation; inRecent advances in developmental biology of animals (eds) S C Goel and C B L Srivastava (Pune: Indian Society of Developmental biologists) pp 175–177

    Google Scholar 

  • Tabin C J 1991 Retinoids, homeoboxes and growth factors: toward molecular models for limb development;Cell 66 199–217

    Article  PubMed  CAS  Google Scholar 

  • Takekoshi S 1964 The mechanism of vitamin A induced teratogenesis;J. Embryol. Exp. Morphol. 12 263–271

    PubMed  CAS  Google Scholar 

  • Taylor S C and Kollros J J 1946 Stages in the normal development ofRana pipiens larvae;Anat. Rec. 94 7–23

    Article  Google Scholar 

  • Thoms S D and Stocum D L 1984 Retinoic acid induced pattern duplication in regenerating urodele limbs;Dev. Biol. 103 319–328

    Article  PubMed  CAS  Google Scholar 

  • Thornton C S 1968 Amphibian limb regeneration; inAdvances in morphogenesis (eds) M Abercombie and J Brachet (London: Academic Press) vol. 7, pp 205–219

    Google Scholar 

  • Tickle C 1992 A tool for transgenesis;Nature (London) 358 188–189

    Article  CAS  Google Scholar 

  • Vasan N S 1981 Proteoglycan synthesis by sternal chondrocytes perturbed with vitamin A;J. Embryol. Exp. Morphol. 63 181–191

    PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. I. A. Niaze

    Present address: , D-2/2276, Vasant Kunj, 110070, New Delhi, India

Authors and Affiliations

  1. Department of Zoology, University of Rajasthan, 302004, Jaipur, India

    I. A. Niaze

Authors
  1. I. A. Niaze
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Niaze, I.A. Background to work on retinoids and amphibian limb regeneration: Studies on anuran tadpoles—a retrospect. J Biosci 21, 273–297 (1996). https://doi.org/10.1007/BF02703089

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02703089

Keywords

Search

Navigation