Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1996 May 1;133(3):631–646. doi: 10.1083/jcb.133.3.631

Neurotrophins promote the survival and development of neurons in the cerebellum of hypothyroid rats in vivo

PMCID: PMC2120825  PMID: 8636237

Abstract

The development of cerebellar cortex is strongly impaired by thyroid hormone (T3) deficiency, leading to altered migration, differentiation, synaptogenesis, and survival of neurons. To determine whether alteration in the expression of neurotrophins and/or their receptors may contribute to these impairments, we first analyzed their expression using a sensitive RNAse protection assay and in situ hybridization; second, we administered the deficient neurotrophins to hypothyroid animals. We found that early hypothyroidism disrupted the developmental pattern of expression of the four neurotrophins, leading to relatively higher levels of NGF and neurotrophin 4/5 mRNAs and to a severe deficit in NT-3 and brain-derived neurotrophic factor (BDNF) mRNA expression, without alteration in the levels of the full-length tyrosine kinase (trk) B and trkC receptor mRNAs. Grafting of P3 hypothyroid rats with cell lines expressing high levels of neurotrophin 3 (NT-3) or BDNF prevented hypothyroidism-induced cell death in neurons of the internal granule cell layer at P15. In addition, we found that NT-3, but not BDNF, induced the differentiation and/or migration of neurons in the external granule cell layer, stimulated the elaboration of the dendritic tree by Purkinje cells, and promoted the formation of the mature pattern of synaptic afferents to Purkinje cell somas. Thus, our results indicate that both granule and Purkinje neurons require appropriate levels of NT-3 for normal development in vivo and suggest that T3 may regulate the levels of neurotrophins to promote the development of cerebellum.

Full Text

The Full Text of this article is available as a PDF (4.8 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altman J. Postnatal development of the cerebellar cortex in the rat. 3. Maturation of the components of the granular layer. J Comp Neurol. 1972 Aug;145(4):465–513. doi: 10.1002/cne.901450403. [DOI] [PubMed] [Google Scholar]
  2. Altman J. Postnatal development of the cerebellar cortex in the rat. I. The external germinal layer and the transitional molecular layer. J Comp Neurol. 1972 Jul;145(3):353–397. doi: 10.1002/cne.901450305. [DOI] [PubMed] [Google Scholar]
  3. Altman J. Postnatal development of the cerebellar cortex in the rat. II. Phases in the maturation of Purkinje cells and of the molecular layer. J Comp Neurol. 1972 Aug;145(4):399–463. doi: 10.1002/cne.901450402. [DOI] [PubMed] [Google Scholar]
  4. Arenas E., Persson H. Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo. Nature. 1994 Jan 27;367(6461):368–371. doi: 10.1038/367368a0. [DOI] [PubMed] [Google Scholar]
  5. Arends M. J., Morris R. G., Wyllie A. H. Apoptosis. The role of the endonuclease. Am J Pathol. 1990 Mar;136(3):593–608. [PMC free article] [PubMed] [Google Scholar]
  6. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  7. Baptista C. A., Hatten M. E., Blazeski R., Mason C. A. Cell-cell interactions influence survival and differentiation of purified Purkinje cells in vitro. Neuron. 1994 Feb;12(2):243–260. doi: 10.1016/0896-6273(94)90268-2. [DOI] [PubMed] [Google Scholar]
  8. Barbacid M. Nerve growth factor: a tale of two receptors. Oncogene. 1993 Aug;8(8):2033–2042. [PubMed] [Google Scholar]
  9. Barbacid M. The Trk family of neurotrophin receptors. J Neurobiol. 1994 Nov;25(11):1386–1403. doi: 10.1002/neu.480251107. [DOI] [PubMed] [Google Scholar]
  10. Barde Y. A., Edgar D., Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982;1(5):549–553. doi: 10.1002/j.1460-2075.1982.tb01207.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Barker P. A., Shooter E. M. Disruption of NGF binding to the low affinity neurotrophin receptor p75LNTR reduces NGF binding to TrkA on PC12 cells. Neuron. 1994 Jul;13(1):203–215. doi: 10.1016/0896-6273(94)90470-7. [DOI] [PubMed] [Google Scholar]
  12. Benedetti M., Levi A., Chao M. V. Differential expression of nerve growth factor receptors leads to altered binding affinity and neurotrophin responsiveness. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7859–7863. doi: 10.1073/pnas.90.16.7859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Berkemeier L. R., Winslow J. W., Kaplan D. R., Nikolics K., Goeddel D. V., Rosenthal A. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron. 1991 Nov;7(5):857–866. doi: 10.1016/0896-6273(91)90287-a. [DOI] [PubMed] [Google Scholar]
  14. Bradley D. J., Young W. S., 3rd, Weinberger C. Differential expression of alpha and beta thyroid hormone receptor genes in rat brain and pituitary. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7250–7254. doi: 10.1073/pnas.86.18.7250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cabelli R. J., Hohn A., Shatz C. J. Inhibition of ocular dominance column formation by infusion of NT-4/5 or BDNF. Science. 1995 Mar 17;267(5204):1662–1666. doi: 10.1126/science.7886458. [DOI] [PubMed] [Google Scholar]
  16. Chao M. V., Hempstead B. L. p75 and Trk: a two-receptor system. Trends Neurosci. 1995 Jul;18(7):321–326. [PubMed] [Google Scholar]
  17. Charrasse S., Jehan F., Confort C., Brachet P., Clos J. Thyroid hormone promotes transient nerve growth factor synthesis in rat cerebellar neuroblasts. Dev Neurosci. 1992;14(4):282–289. doi: 10.1159/000111673. [DOI] [PubMed] [Google Scholar]
  18. Confort C., Charrasse S., Clos J. Nerve growth factor enhances DNA synthesis in cultured cerebellar neuroblasts. Neuroreport. 1991 Oct;2(10):566–568. doi: 10.1097/00001756-199110000-00003. [DOI] [PubMed] [Google Scholar]
  19. Ernfors P., Ibáez C. F., Ebendal T., Olson L., Persson H. Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5454–5458. doi: 10.1073/pnas.87.14.5454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ernfors Patrik, Merlio Jean-Phillipe, Persson Håkan. Cells Expressing mRNA for Neurotrophins and their Receptors During Embryonic Rat Development. Eur J Neurosci. 1992 Oct;4(11):1140–1158. doi: 10.1111/j.1460-9568.1992.tb00141.x. [DOI] [PubMed] [Google Scholar]
  21. Figueiredo B. C., Almazan G., Ma Y., Tetzlaff W., Miller F. D., Cuello A. C. Gene expression in the developing cerebellum during perinatal hypo- and hyperthyroidism. Brain Res Mol Brain Res. 1993 Mar;17(3-4):258–268. doi: 10.1016/0169-328x(93)90010-m. [DOI] [PubMed] [Google Scholar]
  22. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gao W. Q., Zheng J. L., Karihaloo M. Neurotrophin-4/5 (NT-4/5) and brain-derived neurotrophic factor (BDNF) act at later stages of cerebellar granule cell differentiation. J Neurosci. 1995 Apr;15(4):2656–2667. doi: 10.1523/JNEUROSCI.15-04-02656.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Garner A. S., Large T. H. Isoforms of the avian TrkC receptor: a novel kinase insertion dissociates transformation and process outgrowth from survival. Neuron. 1994 Aug;13(2):457–472. doi: 10.1016/0896-6273(94)90360-3. [DOI] [PubMed] [Google Scholar]
  25. Gavrieli Y., Sherman Y., Ben-Sasson S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. doi: 10.1083/jcb.119.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ghosh A., Greenberg M. E. Distinct roles for bFGF and NT-3 in the regulation of cortical neurogenesis. Neuron. 1995 Jul;15(1):89–103. doi: 10.1016/0896-6273(95)90067-5. [DOI] [PubMed] [Google Scholar]
  27. Hallbök F., Ibáez C. F., Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron. 1991 May;6(5):845–858. doi: 10.1016/0896-6273(91)90180-8. [DOI] [PubMed] [Google Scholar]
  28. Hantzopoulos P. A., Suri C., Glass D. J., Goldfarb M. P., Yancopoulos G. D. The low affinity NGF receptor, p75, can collaborate with each of the Trks to potentiate functional responses to the neurotrophins. Neuron. 1994 Jul;13(1):187–201. doi: 10.1016/0896-6273(94)90469-3. [DOI] [PubMed] [Google Scholar]
  29. Heisenberg C. P., Thoenen H., Lindholm D. Tri-iodothyronine regulates survival and differentiation of rat cerebellar granule neurons. Neuroreport. 1992 Aug;3(8):685–688. doi: 10.1097/00001756-199208000-00008. [DOI] [PubMed] [Google Scholar]
  30. Hohn A., Leibrock J., Bailey K., Barde Y. A. Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature. 1990 Mar 22;344(6264):339–341. doi: 10.1038/344339a0. [DOI] [PubMed] [Google Scholar]
  31. Ip N. Y., Ibáez C. F., Nye S. H., McClain J., Jones P. F., Gies D. R., Belluscio L., Le Beau M. M., Espinosa R., 3rd, Squinto S. P. Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3060–3064. doi: 10.1073/pnas.89.7.3060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Jahn R., Schiebler W., Ouimet C., Greengard P. A 38,000-dalton membrane protein (p38) present in synaptic vesicles. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4137–4141. doi: 10.1073/pnas.82.12.4137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Johnson E. M., Jr, Taniuchi M., DiStefano P. S. Expression and possible function of nerve growth factor receptors on Schwann cells. Trends Neurosci. 1988 Jul;11(7):299–304. doi: 10.1016/0166-2236(88)90090-2. [DOI] [PubMed] [Google Scholar]
  34. Jones K. R., Fariñas I., Backus C., Reichardt L. F. Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell. 1994 Mar 25;76(6):989–999. doi: 10.1016/0092-8674(94)90377-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Jones K. R., Reichardt L. F. Molecular cloning of a human gene that is a member of the nerve growth factor family. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8060–8064. doi: 10.1073/pnas.87.20.8060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kaisho Y., Yoshimura K., Nakahama K. Cloning and expression of a cDNA encoding a novel human neurotrophic factor. FEBS Lett. 1990 Jun 18;266(1-2):187–191. doi: 10.1016/0014-5793(90)81536-w. [DOI] [PubMed] [Google Scholar]
  37. Klein R., Conway D., Parada L. F., Barbacid M. The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain. Cell. 1990 May 18;61(4):647–656. doi: 10.1016/0092-8674(90)90476-u. [DOI] [PubMed] [Google Scholar]
  38. Krueger B. K., Burne J. F., Raff M. C. Evidence for large-scale astrocyte death in the developing cerebellum. J Neurosci. 1995 May;15(5 Pt 1):3366–3374. doi: 10.1523/JNEUROSCI.15-05-03366.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Kubo T., Nonomura T., Enokido Y., Hatanaka H. Brain-derived neurotrophic factor (BDNF) can prevent apoptosis of rat cerebellar granule neurons in culture. Brain Res Dev Brain Res. 1995 Apr 18;85(2):249–258. doi: 10.1016/0165-3806(94)00220-t. [DOI] [PubMed] [Google Scholar]
  40. Lamballe F., Tapley P., Barbacid M. trkC encodes multiple neurotrophin-3 receptors with distinct biological properties and substrate specificities. EMBO J. 1993 Aug;12(8):3083–3094. doi: 10.1002/j.1460-2075.1993.tb05977.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Large T. H., Bodary S. C., Clegg D. O., Weskamp G., Otten U., Reichardt L. F. Nerve growth factor gene expression in the developing rat brain. Science. 1986 Oct 17;234(4774):352–355. doi: 10.1126/science.3764415. [DOI] [PubMed] [Google Scholar]
  42. Laurenzi M. A., Barbany G., Timmusk T., Lindgren J. A., Persson H. Expression of mRNA encoding neurotrophins and neurotrophin receptors in rat thymus, spleen tissue and immunocompetent cells. Regulation of neurotrophin-4 mRNA expression by mitogens and leukotriene B4. Eur J Biochem. 1994 Aug 1;223(3):733–741. doi: 10.1111/j.1432-1033.1994.tb19047.x. [DOI] [PubMed] [Google Scholar]
  43. Leclerc N., Beesley P. W., Brown I., Colonnier M., Gurd J. W., Paladino T., Hawkes R. Synaptophysin expression during synaptogenesis in the rat cerebellar cortex. J Comp Neurol. 1989 Feb 8;280(2):197–212. doi: 10.1002/cne.902800204. [DOI] [PubMed] [Google Scholar]
  44. Legrand C., Clos J. Biochemical, immunocytochemical and morphological evidence for an interaction between thyroid hormone and nerve growth factor in the developing cerebellum of normal and hypothyroid rats. Dev Neurosci. 1991;13(6):382–396. doi: 10.1159/000112189. [DOI] [PubMed] [Google Scholar]
  45. Legrand J. Analyse de l'action morphogénétique des hormones thyroïdiennes sur le cervelet du jeune rat. Arch Anat Microsc Morphol Exp. 1967 Jul-Dec;56(3):205–244. [PubMed] [Google Scholar]
  46. Leibrock J., Lottspeich F., Hohn A., Hofer M., Hengerer B., Masiakowski P., Thoenen H., Barde Y. A. Molecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989 Sep 14;341(6238):149–152. doi: 10.1038/341149a0. [DOI] [PubMed] [Google Scholar]
  47. Levi-Montalcini R. The nerve growth factor 35 years later. Science. 1987 Sep 4;237(4819):1154–1162. doi: 10.1126/science.3306916. [DOI] [PubMed] [Google Scholar]
  48. Lewis P. D., Patel A. J., Johnson A. L., Balázs R. Effect of thyroid deficiency on cell acquistion in the postnatal rat brain: a quantitative histological study. Brain Res. 1976 Mar 5;104(1):49–62. doi: 10.1016/0006-8993(76)90646-6. [DOI] [PubMed] [Google Scholar]
  49. Lindefors N., Brodin E., Metsis M. Spatiotemporal selective effects on brain-derived neurotrophic factor and trkB messenger RNA in rat hippocampus by electroconvulsive shock. Neuroscience. 1995 Apr;65(3):661–670. doi: 10.1016/0306-4522(94)00550-o. [DOI] [PubMed] [Google Scholar]
  50. Lindholm D., Castrén E., Tsoulfas P., Kolbeck R., Berzaghi M. da P., Leingärtner A., Heisenberg C. P., Tessarollo L., Parada L. F., Thoenen H. Neurotrophin-3 induced by tri-iodothyronine in cerebellar granule cells promotes Purkinje cell differentiation. J Cell Biol. 1993 Jul;122(2):443–450. doi: 10.1083/jcb.122.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Mahadeo D., Kaplan L., Chao M. V., Hempstead B. L. High affinity nerve growth factor binding displays a faster rate of association than p140trk binding. Implications for multi-subunit polypeptide receptors. J Biol Chem. 1994 Mar 4;269(9):6884–6891. [PubMed] [Google Scholar]
  52. Maisonpierre P. C., Belluscio L., Friedman B., Alderson R. F., Wiegand S. J., Furth M. E., Lindsay R. M., Yancopoulos G. D. NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron. 1990 Oct;5(4):501–509. doi: 10.1016/0896-6273(90)90089-x. [DOI] [PubMed] [Google Scholar]
  53. Masana Y., Wanaka A., Kato H., Asai T., Tohyama M. Localization of trkB mRNA in postnatal brain development. J Neurosci Res. 1993 Aug 1;35(5):468–479. doi: 10.1002/jnr.490350503. [DOI] [PubMed] [Google Scholar]
  54. Mason C. A., Gregory E. Postnatal maturation of cerebellar mossy and climbing fibers: transient expression of dual features on single axons. J Neurosci. 1984 Jul;4(7):1715–1735. doi: 10.1523/JNEUROSCI.04-07-01715.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Mellström B., Naranjo J. R., Santos A., Gonzalez A. M., Bernal J. Independent expression of the alpha and beta c-erbA genes in developing rat brain. Mol Endocrinol. 1991 Sep;5(9):1339–1350. doi: 10.1210/mend-5-9-1339. [DOI] [PubMed] [Google Scholar]
  56. Merlio J. P., Ernfors P., Jaber M., Persson H. Molecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system. Neuroscience. 1992 Dec;51(3):513–532. doi: 10.1016/0306-4522(92)90292-a. [DOI] [PubMed] [Google Scholar]
  57. Middlemas D. S., Lindberg R. A., Hunter T. trkB, a neural receptor protein-tyrosine kinase: evidence for a full-length and two truncated receptors. Mol Cell Biol. 1991 Jan;11(1):143–153. doi: 10.1128/mcb.11.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Mount H. T., Dreyfus C. F., Black I. B. Neurotrophin-3 selectively increases cultured Purkinje cell survival. Neuroreport. 1994 Dec 20;5(18):2497–2500. doi: 10.1097/00001756-199412000-00023. [DOI] [PubMed] [Google Scholar]
  59. Muñoz A., Rodriguez-Peña A., Perez-Castillo A., Ferreiro B., Sutcliffe J. G., Bernal J. Effects of neonatal hypothyroidism on rat brain gene expression. Mol Endocrinol. 1991 Feb;5(2):273–280. doi: 10.1210/mend-5-2-273. [DOI] [PubMed] [Google Scholar]
  60. Nicholson J. L., Altman J. Synaptogenesis in the rat cerebellum: effects of early hypo- and hyperthyroidism. Science. 1972 May 5;176(4034):530–532. doi: 10.1126/science.176.4034.530. [DOI] [PubMed] [Google Scholar]
  61. Nicholson J. L., Altman J. The effects of early hypo- and hyperthyroidism on the development of rat cerebellar cortex. I. Cell proliferation and differentiation. Brain Res. 1972 Sep 15;44(1):13–23. doi: 10.1016/0006-8993(72)90362-9. [DOI] [PubMed] [Google Scholar]
  62. Nicholson J. L., Altman J. The effects of early hypo- and hyperthyroidism on the development of the rat cerebellar cortex. II. Synaptogenesis in the molecular layer. Brain Res. 1972 Sep 15;44(1):25–36. doi: 10.1016/0006-8993(72)90363-0. [DOI] [PubMed] [Google Scholar]
  63. Rabié A., Bréhier A., Intrator S., Clavel M. C., Parkes C. O., Legrand C., Thomasset M. Thyroid state and cholecalcin (calcium-binding protein) in cerebellum of the developing rat. Brain Res. 1986 Oct;394(2):253–265. doi: 10.1016/0165-3806(86)90101-x. [DOI] [PubMed] [Google Scholar]
  64. Radeke M. J., Misko T. P., Hsu C., Herzenberg L. A., Shooter E. M. Gene transfer and molecular cloning of the rat nerve growth factor receptor. Nature. 1987 Feb 12;325(6105):593–597. doi: 10.1038/325593a0. [DOI] [PubMed] [Google Scholar]
  65. Rebière A., Dainat J. Répersuccions de l'hypothyroïdie sur la synaptogenèse dans le cortex eérébelleux du rat. Etude quantitative de l'influence des hormones thyroïdiennes en fonction de l'âge. Acta Neuropathol. 1976 Jun 15;35(2):117–129. doi: 10.1007/BF00690558. [DOI] [PubMed] [Google Scholar]
  66. Rocamora N., García-Ladona F. J., Palacios J. M., Mengod G. Differential expression of brain-derived neurotrophic factor, neurotrophin-3, and low-affinity nerve growth factor receptor during the postnatal development of the rat cerebellar system. Brain Res Mol Brain Res. 1993 Jan;17(1-2):1–8. doi: 10.1016/0169-328x(93)90065-w. [DOI] [PubMed] [Google Scholar]
  67. Rosenthal A., Goeddel D. V., Nguyen T., Lewis M., Shih A., Laramee G. R., Nikolics K., Winslow J. W. Primary structure and biological activity of a novel human neurotrophic factor. Neuron. 1990 May;4(5):767–773. doi: 10.1016/0896-6273(90)90203-r. [DOI] [PubMed] [Google Scholar]
  68. Segal R. A., Pomeroy S. L., Stiles C. D. Axonal growth and fasciculation linked to differential expression of BDNF and NT3 receptors in developing cerebellar granule cells. J Neurosci. 1995 Jul;15(7 Pt 1):4970–4981. doi: 10.1523/JNEUROSCI.15-07-04970.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Segal R. A., Takahashi H., McKay R. D. Changes in neurotrophin responsiveness during the development of cerebellar granule neurons. Neuron. 1992 Dec;9(6):1041–1052. doi: 10.1016/0896-6273(92)90064-k. [DOI] [PubMed] [Google Scholar]
  70. Snider W. D., Johnson E. M., Jr Neurotrophic molecules. Ann Neurol. 1989 Oct;26(4):489–506. doi: 10.1002/ana.410260402. [DOI] [PubMed] [Google Scholar]
  71. Sotelo C., Bourrat F., Triller A. Postnatal development of the inferior olivary complex in the rat. II. Topographic organization of the immature olivocerebellar projection. J Comp Neurol. 1984 Jan 10;222(2):177–199. doi: 10.1002/cne.902220204. [DOI] [PubMed] [Google Scholar]
  72. Strait K. A., Schwartz H. L., Seybold V. S., Ling N. C., Oppenheimer J. H. Immunofluorescence localization of thyroid hormone receptor protein beta 1 and variant alpha 2 in selected tissues: cerebellar Purkinje cells as a model for beta 1 receptor-mediated developmental effects of thyroid hormone in brain. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3887–3891. doi: 10.1073/pnas.88.9.3887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Tessarollo L., Tsoulfas P., Martin-Zanca D., Gilbert D. J., Jenkins N. A., Copeland N. G., Parada L. F. trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues. Development. 1993 Jun;118(2):463–475. doi: 10.1242/dev.118.2.463. [DOI] [PubMed] [Google Scholar]
  74. Timmusk T., Belluardo N., Metsis M., Persson H. Widespread and developmentally regulated expression of neurotrophin-4 mRNA in rat brain and peripheral tissues. Eur J Neurosci. 1993 Jun 1;5(6):605–613. doi: 10.1111/j.1460-9568.1993.tb00526.x. [DOI] [PubMed] [Google Scholar]
  75. Timmusk T., Palm K., Metsis M., Reintam T., Paalme V., Saarma M., Persson H. Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron. 1993 Mar;10(3):475–489. doi: 10.1016/0896-6273(93)90335-o. [DOI] [PubMed] [Google Scholar]
  76. Tsoulfas P., Soppet D., Escandon E., Tessarollo L., Mendoza-Ramirez J. L., Rosenthal A., Nikolics K., Parada L. F. The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC12 cells. Neuron. 1993 May;10(5):975–990. doi: 10.1016/0896-6273(93)90212-a. [DOI] [PubMed] [Google Scholar]
  77. Valenzuela D. M., Maisonpierre P. C., Glass D. J., Rojas E., Nuñez L., Kong Y., Gies D. R., Stitt T. N., Ip N. Y., Yancopoulos G. D. Alternative forms of rat TrkC with different functional capabilities. Neuron. 1993 May;10(5):963–974. doi: 10.1016/0896-6273(93)90211-9. [DOI] [PubMed] [Google Scholar]
  78. Verdi J. M., Birren S. J., Ibáez C. F., Persson H., Kaplan D. R., Benedetti M., Chao M. V., Anderson D. J. p75LNGFR regulates Trk signal transduction and NGF-induced neuronal differentiation in MAH cells. Neuron. 1994 Apr;12(4):733–745. doi: 10.1016/0896-6273(94)90327-1. [DOI] [PubMed] [Google Scholar]
  79. Vicario-Abejón C., Johe K. K., Hazel T. G., Collazo D., McKay R. D. Functions of basic fibroblast growth factor and neurotrophins in the differentiation of hippocampal neurons. Neuron. 1995 Jul;15(1):105–114. doi: 10.1016/0896-6273(95)90068-3. [DOI] [PubMed] [Google Scholar]
  80. Westin G., Gerster T., Müller M. M., Schaffner G., Schaffner W. OVEC, a versatile system to study transcription in mammalian cells and cell-free extracts. Nucleic Acids Res. 1987 Sep 11;15(17):6787–6798. doi: 10.1093/nar/15.17.6787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Wiedenmann B., Franke W. W. Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles. Cell. 1985 Jul;41(3):1017–1028. doi: 10.1016/s0092-8674(85)80082-9. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES