The nerve growth factor 35 years later.

"Embryogenesis is in some way a model system. It has always been distinguished by the exactitude even punctitio, of its anatomical descriptions. An experiment by one of the great masters of embryology could be made the text of a discourse on scientific method. But something is wrong, or has been wrong. There is no theory of development in the sense in which Mendelism is a theory that accounts for the results of breeding experiments. There has therefore been little sense of progression or timeliness about embryological research. Of many papers delivered at embryological meetings, however good they may be in themselves . . . one too often feels that they might have been delivered five years beforehand without making anyone much the wiser, or deferred for five years without making anyone conscious of a great loss" (1). This feeling of frustration so incisively conveyed by these considerations by P. Medawar, pervaded, in the forties, the field of experimental embryology which had been enthusiastically acclaimed in the mid-thirties, when the upper lip of the amphibian blastopore brought this area of research to the forefront of the biological stage. The side branch of experimental neuroembryology, which had stemmed out from the common tree and was entirely devoted to the study of the tropic interrelations between neuronal cell populations and between these and the innervated organs and tissues, was then in its initial vigorous growth phase. It in turn suffered from a sharp decrease in the enthusiasm that had inflamed the pioneers in this field, ever since R. G. Harrison delivered his celebrated lecture on this topic at the Royal Society in London in 1935 (2). Although the alternate "wax and wane" cycles are the rule rather than the exception in all fields of human endeavor, in that of biological sciences the "wane" is all too often indicative of a justified loss of faith in the rational and methodical approach that had at first raised so much hope. A brief account of the state-of-the-art of experimental neuroembryology in the

[1]  Peter Medawar,et al.  The art of the soluble , 2021, Nature.

[2]  L. F. Kromer Nerve growth factor treatment after brain injury prevents neuronal death. , 1987, Science.

[3]  R. Mains,et al.  Peptides in the nervous system , 1986, Trends in Neurosciences.

[4]  Pietro Calissano,et al.  Nerve growth factor as a paradigm for other polypeptide growth factors , 1986, Trends in Neurosciences.

[5]  F. Gage,et al.  Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[6]  E. Alleva,et al.  Aggressive behavior induces release of nerve growth factor from mouse salivary gland into the bloodstream. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[7]  L. Reichardt,et al.  Studies on the expression of the beta nerve growth factor (NGF) gene in the central nervous system: level and regional distribution of NGF mRNA suggest that NGF functions as a trophic factor for several distinct populations of neurons. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[8]  G. Weskamp,et al.  Nerve growth factor induces mast cell degranulation without changing intracellular calcium levels , 1986, FEBS letters.

[9]  L. Olson,et al.  Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[10]  W. Rutter,et al.  Differential RNA splicing predicts two distinct nerve growth factor precursors , 1986, Nature.

[11]  P. Claude,et al.  Nerve growth factor is a mitogen for cultured chromaffin cells , 1985, Nature.

[12]  D. Bar-Sagi,et al.  Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation , 1985, Cell.

[13]  R. Levi‐montalcini,et al.  Differentiating effects of murine nerve growth factor in the peripheral and central nervous systems of Xenopus laevis tadpoles. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[14]  S. Alemà,et al.  Differentiation of PC12 phaeochromocytoma cells induced by v-src oncogene , 1985, Nature.

[15]  M. Johnston,et al.  Choline acetyltransferase activity in striatum of neonatal rats increased by nerve growth factor. , 1985, Science.

[16]  Charles J. Sherr,et al.  The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF 1 , 1985, Cell.

[17]  C. Cozzari,et al.  Cyclocytidine-induced release of nerve growth factor from mouse submandibular glands enhances regeneration of sympathetic fibers in adult mice , 1985, Brain Research.

[18]  K. Sugiyama,et al.  Histamine-release induced by 7S nerve-growth factor of mouse submandibular salivary glands. , 1985, Archives of oral biology.

[19]  R. Evans,et al.  Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product , 1985, Nature.

[20]  Eugene M. Johnson,et al.  Central nervous system and peripheral nerve growth factor provide trophic support critical to mature sensory neuronal survival , 1985, Nature.

[21]  D. Lawrence,et al.  Chemical mutation of enzyme active sites. , 1984, Science.

[22]  A. Cattaneo,et al.  The nerve growth factor: Established findings and controversial aspects , 1984 .

[23]  M. Schwab,et al.  Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basalis in the rat , 1984, Brain Research.

[24]  F. Hefti,et al.  Chronic intraventricular injections of nerve growth factor elevate hippocampal choline acetyltransferase activity in adult rats with partial septo-hippocampal lesions , 1984, Brain Research.

[25]  A. Ullrich,et al.  Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences , 1984, Nature.

[26]  D. J. Beer,et al.  The influence of histamine on immune and inflammatory responses. , 1984, Advances in immunology.

[27]  U. Francke,et al.  The human gene for the beta subunit of nerve growth factor is located on the proximal short arm of chromosome 1. , 1983, Science.

[28]  R F Doolittle,et al.  Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. , 1983, Science.

[29]  M. Schwab,et al.  NGF-mediated increase of choline acetyltransferase (ChAT) in the neonatal rat forebrain: evidence for a physiological role of NGF in the brain? , 1983, Brain research.

[30]  A. Ullrich,et al.  Human β-nerve growth factor gene sequence highly homologous to that of mouse , 1983, Nature.

[31]  W. Rutter,et al.  Isolation and nucleotide sequence of a cDNA encoding the precursor of mouse nerve growth factor , 1983, Nature.

[32]  L. Greene,et al.  Regulation of a high molecular weight microtubule-associated protein in PC12 cells by nerve growth factor , 1983, The Journal of cell biology.

[33]  L. Greene,et al.  Nerve growth factor has both mitogenic and antimitogenic activity. , 1982, Developmental biology.

[34]  R. Campenot,et al.  Development of sympathetic neurons in compartmentalized cultures. II. Local control of neurite survival by nerve growth factor. , 1982, Developmental biology.

[35]  A. Bruni,et al.  Interaction between nerve growth factor and lysophosphatidylserine on rat peritoneal mast cells , 1982, FEBS letters.

[36]  M. P. Johnson,et al.  Nerve growth factor stimulates phospholipid methylation in growing neurites. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[37]  C. Cozzari,et al.  Somatic and behavioural postnatal effects of fetal injections of nerve growth factor antibodies in the rat , 1981, Nature.

[38]  R. W. Gundersen,et al.  Characterization of the turning response of dorsal root neurites toward nerve growth factor , 1980, The Journal of cell biology.

[39]  J. Pearson,et al.  Dorsal root ganglion neurons are destroyed by exposure in utero to maternal antibody to nerve growth factor. , 1980, Science.

[40]  M. Schwab,et al.  Immunosympathectomy: Lack of evidence for a complement-mediated cytotoxic mechanism , 1980, Brain Research.

[41]  E. Hackenthal,et al.  Renin in the submaxillary gland: a review. , 1980, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[42]  L. Olson,et al.  Nerve growth factors in the rat iris , 1980, Nature.

[43]  H. Thoenen,et al.  The Distribution of Nerve Growth Factor in the Male Sex Organs of Mammals , 1980, Journal of neurochemistry.

[44]  R. Levi‐montalcini,et al.  Comparative studies on testosterone and L-thyroxine effects on the synthesis of nerve growth factor in mouse submaxillary salivary glands. , 1980, Experimental cell research.

[45]  E. Shooter,et al.  The nerve growth factor: biochemistry, synthesis, and mechanism of action. , 1980, Annual review of neuroscience.

[46]  R. W. Gundersen,et al.  Neuronal chemotaxis: chick dorsal-root axons turn toward high concentrations of nerve growth factor. , 1979, Science.

[47]  G. Burnstock,et al.  Guinea pig prostate is a rich source of nerve growth factor , 1979, Nature.

[48]  R. Levi‐montalcini,et al.  Nerve growth factor-induced transformation of immature chromaffin cells in vivo into sympathetic neurons: effect of antiserum to nerve growth factor. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[49]  H. Thoenen,et al.  Nerve growth factor-induced fiber outgrowth from isolated rat adrenal chromaffin cells: impairment by glucocorticoids. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[50]  R. Levi‐montalcini,et al.  Sympathetic nerve fibers ingrowth in the central nervous system of neonatal rodent upon intracerebral NGF injections. , 1978, Archives italiennes de biologie.

[51]  Steven B Marston Contractile systems in non-muscle tissues: edited by S. V. Perry, A. Margreth and R. S. Adelstein, published by North- Holland, Amsterdam, 1977. Dfl. 80.− ($32.75) (xi + 360 pages) , 1977 .

[52]  M. Schwab,et al.  Selective induction of tyrosine hydroxylase and dopamine β-hydroxylase by nerve growth factor: comparison between adrenal medulla and sympathetic ganglia of adult and newborn rats , 1977, Brain Research.

[53]  R. Levi‐montalcini,et al.  Mast cells increase in tissues of neonatal rats injected with the nerve growth factor , 1977, Brain Research.

[54]  L. Greene,et al.  Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[55]  R. Bradshaw,et al.  Subcellular localization of nerve growth factor receptors. Thirteen-day chick embryo brain. , 1976, The Journal of biological chemistry.

[56]  R. Levi‐montalcini The nerve growth factor: its role in growth, differentiation and function of the sympathetic adrenergic neuron. , 1976, Progress in brain research.

[57]  V. Hamburger Changing Concepts in Developmental Neurobiology , 2015, Perspectives in biology and medicine.

[58]  E. Mugnaini,et al.  Light and electron microscopic studies on the excessive growth of sympathetic ganglia in rats injected daily from birth with 6-OHDA and NGF. , 1975, Archives Italiennes de Biologie.

[59]  I. Hendry The response of adrenergic neurones to axotomy and nerve growth factor , 1975, Brain Research.

[60]  I. Hendry The effects of axotomy on the development of the rat superior cervical ganglion , 1975, Brain Research.

[61]  H. Thoenen,et al.  Biological importance of retrograde axonal transport of nerve growth factor in adrenergic neurons , 1975, Brain Research.

[62]  F. Oesch,et al.  Nerve growth factor induces volume increase and enhances tyrosine hydroxylase synthesis in chemically axotomized sympathetic ganglia of newborn rats. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[63]  E. Shooter,et al.  The Biological Activity of Cross-Linked β Nerve Growth Factor Protein , 1974 .

[64]  K. Stöckel,et al.  Specificity of the retrograde axonal transport of nerve growth factor. , 1974, Brain research.

[65]  R. Angeletti,et al.  Nerve growth factor from mouse submaxillary gland: amino acid sequence. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[66]  H. Thoenen,et al.  Selective induction by nerve growth factor of tyrosine hydroxylase and dopamine- -hydroxylase in the rat superior cervical ganglia. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[67]  R. Levi‐montalcini,et al.  Sympathetic nerve cell destruction in newborn mammals by 6-hydroxydopamine. , 1970, Proceedings of the National Academy of Sciences of the United States of America.

[68]  V. Bocchini,et al.  The nerve growth factor: purification as a 30,000-molecular-weight protein. , 1969, Proceedings of the National Academy of Sciences of the United States of America.

[69]  D. Young Nerve growth factor , 1968 .

[70]  E. Shooter,et al.  The isolation of the mouse nerve growth factor protein in a high molecular weight form. , 1967, Biochemistry.

[71]  R. Levi‐montalcini The nerve growth factor: its mode of action on sensory and sympathetic nerve cells. , 1966, Harvey lectures.

[72]  R. Levi‐montalcini GROWTH CONTROL OF NERVE CELLS BY A PROTEIN FACTOR AND ITS ANTISERUM: DISCOVERY OF THIS FACTOR MAY PROVIDE NEW LEADS TO UNDERSTANDING OF SOME NEUROGENETIC PROCESSES. , 1964, Science.

[73]  R. Levi‐montalcini,et al.  Essential role of the nerve growth factor in the survival and maintenance of dissociated sensory and sympathetic embryonic nerve cells in vitro. , 1963, Developmental biology.

[74]  S. Cohen,et al.  PURIFICATION OF A NERVE-GROWTH PROMOTING PROTEIN FROM THE MOUSE SALIVARY GLAND AND ITS NEURO-CYTOTOXIC ANTISERUM. , 1960, Proceedings of the National Academy of Sciences of the United States of America.

[75]  R. Levi‐montalcini,et al.  Destruction of the sympathetic ganglia in mammals by an antiserum to a nerve-growth protein* , 1960, Proceedings of the National Academy of Sciences.

[76]  R. Levi‐montalcini,et al.  EXCESSIVE GROWTH OF THE SYMPATHETIC GANGLIA EVOKED BY A PROTEIN ISOLATED FROM MOUSE SALIVARY GLANDS. , 1960, Proceedings of the National Academy of Sciences of the United States of America.

[77]  S. Cohen Purification and metabolic effects of a nerve growth-promoting protein from snake venom. , 1959, The Journal of biological chemistry.

[78]  S. Cohen,et al.  IN VITRO AND IN VIVO EFFECTS OF A NERVE GROWTH-STIMULATING AGENT ISOLATED FROM SNAKE VENOM. , 1956, Proceedings of the National Academy of Sciences of the United States of America.

[79]  S. Cohen,et al.  A NERVE GROWTH-STIMULATING FACTOR ISOLATED FROM SNAKE VENOM. , 1956, Proceedings of the National Academy of Sciences of the United States of America.

[80]  V. Hamburger,et al.  A NERVE GROWTH-STIMULATING FACTOR ISOLATED FROM SARCOM AS 37 AND 180. , 1954, Proceedings of the National Academy of Sciences of the United States of America.

[81]  V. Hamburger,et al.  A diffusible agent of mouse sarcoma, producing hyperplasia of sympathetic ganglia and hyperneurotization of viscera in the chick embryo , 1953 .

[82]  R. Levi‐montalcini EFFECTS OF MOUSE TUMOR TRANSPLANTATION ON THE NERVOUS SYSTEM , 1952, Annals of the New York Academy of Sciences.

[83]  V. Hamburger,et al.  Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. , 1951, The Journal of experimental zoology.

[84]  R. Levi‐montalcini,et al.  The development of the acoustico‐vestibular centres in the chick embryo in the absence of the afferent root fibers and of descending fiber tracts , 1949, The Journal of comparative neurology.

[85]  V. Hamburger,et al.  Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions. , 1949, The Journal of experimental zoology.

[86]  E. D. Bueker Implantation of tumors in the hind limb field of the embryonic chick and the developmental response of the lumbosacral nervous system , 1948, The Anatomical record.

[87]  R. G. Harrison,et al.  The Croonian Lecture: On the Origin and Development of the Nervous System Studied by the Methods of Experimental Embryology , 1935 .