Skip to main content
Log in

Rita Levi-Montalcini and her major contribution to neurobiology

  • Review
  • Published:
Rendiconti Lincei. Scienze Fisiche e Naturali Aims and scope Submit manuscript

Abstract

In this paper, I shall illustrate the personality of Rita Levi-Montalcini and highlight how she first emerged within a prestigious school, while under the direction of Giuseppe Levi, a most inspiring and stimulating figure. Between 1919 and 1938, he created a rich environment capable of influencing the minds of innumerable students; among them, three future Nobel Prize winners, Renato Dulbecco, Salvador Luria, and Rita Levi-Montalcini, who were companions in the same classroom. In 1938, due to the racial laws for the defence of the race, Luria and Levi-Montalcini were banned from entering the university premises. In a small working space in her bedroom—“a minuscule laboratory not unlike a convent cell”—Levi-Montalcini, supported by Levi, made a most outstanding discovery that opened a new chapter in neurobiology. Further collaborations with Viktor Hamburger and Stanley Cohen led Levi-Montalcini to the discovery of the nerve growth factor (NGF): a remarkable accomplishment which turned out to represent a milestone in the development of modern cell biology.

Graphical abstract

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Courtesy of Historical Archive of the University of Turin

Fig. 2

Courtesy of Piera Levi-Montalcini

Fig. 3

Courtesy of Historical Archive of the University of Turin

Fig. 4
Fig. 5

Courtesy of Piera Levi-Montalcini

Fig. 6

Courtesy of Giacomo Giacobini

Fig. 7

https://hpsrepository.asu.edu/handle/10776/3264?show=full

Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Courtesy of EBRI

Fig. 13

Courtesy of EBRI

Fig. 14

Courtesy of EBRI

Similar content being viewed by others

References

  • Angeletti PU, Levi-Montalcini R, Calissano P (1968) The nerve growth factor (NGF): chemical properties and metabolic effects. Adv Enzymol Relat Areas Mol Biol 31:51–75

    CAS  Google Scholar 

  • Brunso-Bechtold JK, Hamburger V (1979) Retrograde transport of nerve growth factor in chicken embryo. Proc Natl Acad Sci USA 76(3):1494–1496

    Article  CAS  Google Scholar 

  • Bueker ED (1948) Implantation of tumors in the hind limb field of the embryonic chick and the developmental response of the lumbosacral nervous system. Anat Rec 102(3):369–389

    Article  CAS  Google Scholar 

  • Cattaneo A (2013) Immunosympathectomy as the first phenotypic knockout with antibodies. Proc Natl Acad Sci USA 110(13):4877–4885

    Article  CAS  Google Scholar 

  • Chao MV (2010) A conversation with Rita Levi-Montalcini. Annu Rev Physiol 72:1–13

    Article  CAS  Google Scholar 

  • Cohen S (1960) Purification of a nerve-growth promoting protein from the mouse salivary gland and its neurotoxic antiserum. Proc Natl Acad Sci USA 46(3):302–331

    Article  CAS  Google Scholar 

  • Cohen S (1962) Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the newborn animal. J Biol Chem 237:1535–1562

    Google Scholar 

  • Cohen S (2008) Origins of growth factors: NGF and EGF. J Biol Chem 283:33793–33797

    Article  CAS  Google Scholar 

  • Cohen S, Levi-Montalcini R (1956) A nerve growth-stimulating factor isolated from snake venom. Proc Natl Acad Sci USA 42(9):571–574

    Article  CAS  Google Scholar 

  • Cohen S, Levi-Montalcini R, Hamburger V (1954) A nerve growth-stimulating factor isolated from sarcomas 37 and 180. Proc Natl Acad Sci USA 40(10):1014–1018

    Article  CAS  Google Scholar 

  • Cowan WM (1981) Viktor Hamburger’s contribution to developmental neurobiology: an appreciation. In: Cowan WM (ed) Studies in developmental neurobiology: essays in honor of Viktor Hamburger. Oxford University Press, New York, pp 3–21

    Google Scholar 

  • Cowan WM (2001) Viktor Hambuxrger and Rita Levi-Montalcini: the path to the discovery of nerve growth factor. Annu Rev Neurosci 24:551–600

    Article  CAS  Google Scholar 

  • Hamburger V (1925) Über den Einfluss des Nervensystems auf die Entwicklung der Extremitäten von Rana fusca. Wilhelm Roux Arch Entwickl Mech Org 105(1):149–201

    Article  Google Scholar 

  • Hamburger V (1934) The effects of wing bud extirpation on the development of the central nervous system in chick embryo. J Exp Zool 68(3):449–494

    Article  Google Scholar 

  • Hamburger V (1958) Regression versus peripheral control of differentiation in motor hypoplasia. Am J Anat 102(3):365–409

    Article  CAS  Google Scholar 

  • Hamburger V (1975) Cell death in the development of the lateral motor column of the chick embryo. J Comp Neurol 160(4):535–546

    Article  CAS  Google Scholar 

  • Hamburger V (1989) The journey of a neuroembryologist. Annu Rev Neurosci 12:1–12

    Article  CAS  Google Scholar 

  • Hamburger V (1993) The history of the discovery of the nerve growth factor. J Neurobiol 24(7):893–897

    Article  CAS  Google Scholar 

  • Hamburger V (1996) Viktor Hamburger. In: Squire LR (ed) The history of neuroscience in autobiography 1. Society for Neuroscience, Washington, DC, pp 222–250

    Google Scholar 

  • Hamburger V, Levi-Montalcini R (1949) Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions. J Exp Zool 111(3):457–501

    Article  CAS  Google Scholar 

  • Hamburger V, Brunso-Bechtold JK, Yip JW (1981) Neuronal death in the spinal ganglia of the chick embryo and its reduction by nerve growth factor. J Neurosci 1:60–71

    Article  CAS  Google Scholar 

  • Harrison RE (1907) Observations on the living, developing nerve fiber. Anat Rec 1(5):116–118

    Article  Google Scholar 

  • Hogue-Angeletti R, Bradshaw RA (1971) Nerve growth factor from mouse submaxillary gland: amino acid sequence. Proc Natl Acad Sci USA 68(10):2417–2420

    Article  Google Scholar 

  • Hogue-Angeletti R, Mercanti D, Bradshaw RA (1973a) Amino acid sequences of mouse 2.5S nerve growth factor. I. Isolation and characterization of the soluble tryptic and chymotryptic peptides. Biochemistry 12(1):90–100

    Article  Google Scholar 

  • Hogue-Angeletti R, Hermodson MA, Bradshaw RA (1973b) Amino acid sequences of mouse 2.5S nerve growth factor. II. Isolation and characterization of the thermolytic and peptic peptides and the complete covalent structure. Biochemistry 12(1):100–115

    Article  Google Scholar 

  • Hollyday M, Hamburger V (1976) Reduction of the naturally occurring motor neuron loss by enlargement of the periphery. J Comp Neurol 170(3):311–320

    Article  CAS  Google Scholar 

  • Levi G (1945) La struttura della sostanza vivente. Minerva Med 36:81–86

    Google Scholar 

  • Levi G, Meyer H (1941) Nouvelles recherches sur le tissu nerveux cultivé in vitro. Morphologie, croissance et relations réciproques des neurons. Arch Biol (Liège) 52:133–278

    Google Scholar 

  • Levi-Montalcini R (1952) Effects of mouse tumor transplantation on the nervous system. Ann NY Acad Sci 55(2):330–344

    Article  CAS  Google Scholar 

  • Levi-Montalcini R (1975) NGF: an uncharted route. In: Worden FG, Swazey JP, Adelman G (eds) The neurosciences: paths of discovery. MIT Press, Cambridge, pp 245–265

    Google Scholar 

  • Levi-Montalcini R (1982) Developmental neurobiology and the natural history of nerve growth factor. Annu Rev Neurosci 5:341–362

    Article  CAS  Google Scholar 

  • Levi-Montalcini R (1986) Nobel lecture: the nerve growth factor: thirty-five years later. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1986/levi-montalcini-lecture.html. Accessed 3 Oct 2018

  • Levi-Montalcini R (1988) In praise of imperfection: my life and work. Basic Books, New York (It transl: Elogio dell’imperfezione. Garzanti, Milano 1987)

    Google Scholar 

  • Levi-Montalcini R, Booker B (1960a) Destruction of the sympathetic ganglia in mammals by an antiserum to a nerve-growth protein. Proc Natl Acad Sci USA 46(3):384–391

    Article  CAS  Google Scholar 

  • Levi-Montalcini R, Booker B (1960b) Excessive growth of the sympathetic ganglia evoked by a protein isolated from mouse salivary glands. Proc Natl Acad Sci USA 46(3):373–384

    Article  CAS  Google Scholar 

  • Levi-Montalcini R, Hamburger V (1951) Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J Exp Zool 116(2):321–361

    Article  CAS  Google Scholar 

  • Levi-Montalcini R, Hamburger V (1953) A diffusible agent of mouse sarcoma producing hyperplasia of sympathetic ganglia and hyperneurotization of viscera in the chick embyro. J Exp Zool 123(2):233–287

    Article  Google Scholar 

  • Levi-Montalcini R, Levi G (1942) Les conséquences de la destruction d’un territoire d’innervation périphérique sur le développement des centres nerveux correspondants dans l’embryon de Poulet. Arch Biol (Liège) 53:537–545

    Google Scholar 

  • Levi-Montalcini R, Levi G (1943) Recherches quantitatives sur la marche du processus de différenciation des neurons dans les ganglions spinaux de l’embryon de poulet. Arch Biol (Liège) 54:189–206

    Google Scholar 

  • Levi-Montalcini R, Levi G (1944) Correlazioni nello sviluppo tra varie parti del sistema nervoso. I. Conseguenze della demolizione dell’abbozzo di un arto sui centri nervosi nell’embrione di pollo. Comment (Pont Acad Sci), VIII:527–575

  • Levi-Montalcini R, Meyer H, Hamburger V (1954) In vitro experiments on the effects of mouse sarcomas 180 and 37 on the spinal and sympathetic ganglia of the chick embryo. Cancer Res 14(1):49–57

    CAS  Google Scholar 

  • Levi-Montalcini R, Revoltella R, Calissano P (1974) Microtubule proteins in the nerve growth factor mediated response. Interaction between the nerve growth factor and its target cells. Recent Prog Horm Res 30:635–669

    CAS  Google Scholar 

  • Lillie FR (1903) Experimental studies on the development of the organs in the embryo of the fowl (Gallus domesticus). Biol Bull 5(2):92–124

    Article  Google Scholar 

  • Lillie FR (1904) Experimental studies on the development of the organs in the embryo of the fowl (Gallus domesticus). II. The development of defective embryos, and the power of regeneration. Biol Bull 7(1):33–54

    Article  Google Scholar 

  • Lillie FR (1908) The development of the chick: an introduction to embryology. Henry Holt, New York

    Google Scholar 

  • Martinez Arias A, Steventon B (2018) On the nature and function of organizers. Development 145(5):dev159525

    Article  Google Scholar 

  • Martyn I, Kanno TY, Ruzo A, Siggia ED, Brivanlou AH (2018) Self-organization of a human organizer by combined Wnt and nodal signalling. Nature 558:132–135

    Article  CAS  Google Scholar 

  • Oppenheim RW (2001) In memoriam: Viktor Hamburger (1900–2001): journey of a neuroembryologist to the end of the millennium and beyond. Neuron 31(2):179–190

    Article  CAS  Google Scholar 

  • Pourquié O (2018) Human embryonic stem cells get organized. Nature 558:35–36

    Article  Google Scholar 

  • Purves D, Sanes JR (1987) The 1986 Nobel prize in physiology or medicine. Trends Neurosci 10(6):231–235

    Article  CAS  Google Scholar 

  • Scott J, Selby M, Urdea M, Quiroga M, Bell GI, Rutter WJ (1983) Isolation and nucleotide sequence of a cDNA encoding the precursor of mouse nerve growth factor. Nature 302:538–540

    Article  CAS  Google Scholar 

  • Shooter EM (2001) Early days of the nerve growth factor proteins. Annu Rev Neurosci 24:601–629

    Article  CAS  Google Scholar 

  • Shorey ML (1909) The effect of destruction of peripheral areas on the differentiation of the neuroblasts. J Exp Zool 7(1):25–63

    Article  Google Scholar 

  • Shorey ML (1911) A study of the differentiation of neuroblasts in artificial culture media. J Exp Zool 10(1):85–93

    Article  Google Scholar 

  • Spemann H, Mangold H (1924) Über Induktion von Embryonanlagen durch Implantation artfremder Organisatoren. Arch Mikrosk Anat Enwicklmech 100(3–4):599–638

    Google Scholar 

  • Willier BH (1957) Frank Rattray Lillie. Biographical memoirs 30. National Academy of Sciences, Washington, DC, pp 77–236

    Google Scholar 

Download references

Acknowledgements

I would like to thank Prof. Germana Pareti and Dr. Robin Harvey for illuminating discussions, and Maria Romanazzo (Fregi e Majuscole, Turin) not only for copy-editing, but especially for the organization of the whole architecture of text and illustrations. A special mention to Piera Levi-Montalcini for precious information and for help in collecting illustrations. This article is dedicated to my father, Gerolamo Strata, MD, who was sentenced to prison in Savona in the late 30s and then confined to Atripalda (Avellino) for criticism of the fascist regime.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Piergiorgio Strata.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Strata, P. Rita Levi-Montalcini and her major contribution to neurobiology. Rend. Fis. Acc. Lincei 29, 737–753 (2018). https://doi.org/10.1007/s12210-018-0741-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12210-018-0741-4

Keywords

Navigation