Crossref journal-article
Wiley
European Journal of Neuroscience (311)
Abstract

AbstractThe neurotrophin gene family includes four structurally related proteins with neurotrophic activities. Two of them, nerve growth factor and brain‐derived neurotrophic factor (BDNF), have been studied in detail and information has recently emerged on the expression and function of the third member, neurotrophin‐3. In contrast, little information is available on neurotrophin‐4 (NT‐4), the most recently isolated member of this family. In this report we have used a sensitive RNAase protection assay to analyse the developmental expression of NT‐4 mRNA in the rat brain and in 12 different rat peripheral organs. In heart, liver and muscle plus skin NT‐4 mRNA levels were maximal at embryonic day (E) E13 (the earliest time point tested), with reduced levels at later times of development. In lung, kidney and thymus similar levels were seen from E13 to postnatal day (P) 1, with reduced levels in the adult. In testis, ovary and salivary gland NT‐4 mRNA was detected at E16 with a peak shortly after birth. During brain development, NT‐4 mRNA was maximal at E13 followed by a decrease around birth, after which the level increased. The postnatal increase of NT‐4 mRNA was also seen in cerebral cortex and brain stem analysed separately, while in the hippocampus similar levels were found from P1 to adulthood. NT‐4 mRNA was detected in all ten adult rat brain regions analysed with only small regional variations, being highest in pons–medulla, hypothalamus, thalamus and cerebellum. Adult rat thymus, thyroid, muscle, lung and ovary contained higher levels of NT‐4 mRNA than brain, while all other adult tissues showed similar or lower levels than in the brain. The highest level of NT‐4 mRNA overall was found in P1 testis. For comparison, BDNF mRNA was analysed in the same tissues. The expression of BDNF mRNA was in many cases different from that of NT‐4 mRNA. The peak of NT‐4 mRNA expression in several of the peripheral tissues coincided with the peak of naturally occurring neuronal cell death in peripheral ganglia. This is consistent with the possibility that NT‐4 acts as a target‐derived trophic factor in vivo. The widespread and increased expression of NT‐4 mRNA during postnatal brain development could reflect a trophic role of NT‐4 for central nervous system neurons. However, non‐neuronal functions of NT‐4 are also possible, particularly in male and female reproductive tissues, where the NT‐4 protein could function as a growth factor for immature germ cells.

Bibliography

Timmusk, T., Belluardo, N., Metsis, M., & Persson, H. (1993). Widespread and Developmentally Regulated Expression of Neurotrophin‐4 mRNA in Rat Brain and Peripheral Tissues. European Journal of Neuroscience, 5(6), 605–613. Portico.

Authors 4
  1. Tõnis Timmusk (first)
  2. Natale Belluardo (additional)
  3. Madis Metsis (additional)
  4. Håkan Persson (additional)
References 58 Referenced 201
  1. 10.1016/0896-6273(90)90166-D
  2. 10.1002/cne.901280404
  3. 10.1073/pnas.85.8.2628
  4. 10.1126/science.2897715
  5. 10.1016/0014-4886(91)90082-N
  6. 10.1016/0896-6273(89)90040-8
  7. 10.1002/j.1460-2075.1982.tb01207.x
  8. 10.1016/0896-6273(91)90287-A
  9. 10.1021/bi00591a005
  10. 10.1016/0003-2697(87)90021-2
  11. 10.1038/326353a0
  12. 10.1073/pnas.87.14.5454
  13. 10.1016/0896-6273(90)90090-3
  14. 10.1016/0896-6273(91)90084-D
  15. 10.1111/j.1460-9568.1992.tb00141.x
  16. 10.1523/JNEUROSCI.11-06-01577.1991
  17. 10.1111/j.1460-9568.1991.tb00854.x
  18. {'key': 'e_1_2_2_19_1', 'article-title': 'Differential action of neurotrophins in the locus coeruleus and basal forebrain', 'author': 'Friedman W. J.', 'year': '1992', 'journal-title': 'Exp. Neurol.'} / Exp. Neurol. / Differential action of neurotrophins in the locus coeruleus and basal forebrain by Friedman W. J. (1992)
  19. 10.1126/science.2549634
  20. 10.1016/0169-328X(91)90136-L
  21. 10.1016/0896-6273(91)90180-8
  22. 10.1002/j.1460-2075.1984.tb02277.x
  23. 10.1038/331261a0
  24. 10.1002/j.1460-2075.1990.tb07423.x
  25. 10.1038/344339a0
  26. 10.1038/350230a0
  27. 10.1002/j.1460-2075.1991.tb07743.x
  28. {'key': 'e_1_2_2_29_1', 'first-page': '239', 'article-title': 'Expression of neurotrophin‐4 mRNA during oogenesis in Xenopus laevis', 'volume': '36', 'author': 'Ibanez C. F.', 'year': '1992', 'journal-title': 'Int. J. Dev. Biol.'} / Int. J. Dev. Biol. / Expression of neurotrophin‐4 mRNA during oogenesis in Xenopus laevis by Ibanez C. F. (1992)
  29. {'key': 'e_1_2_2_30_1', 'article-title': 'Neurotrophin‐4 is the target‐derived neurotrophic factor for neurons of the trigeminal ganglion', 'author': 'Ibanez C. F.', 'year': '1993', 'journal-title': 'Development'} / Development / Neurotrophin‐4 is the target‐derived neurotrophic factor for neurons of the trigeminal ganglion by Ibanez C. F. (1993)
  30. 10.1073/pnas.89.7.3060
  31. 10.1016/0896-6273(91)90234-Q
  32. 10.1523/JNEUROSCI.06-10-03031.1986
  33. 10.1073/pnas.87.20.8060
  34. 10.1016/0014-5793(90)81536-W
  35. 10.1242/dev.109.4.845
  36. 10.1016/0896-6273(92)90209-V
  37. 10.1073/pnas.88.3.961
  38. 10.1002/j.1460-2075.1985.tb03791.x
  39. 10.1126/science.3764415
  40. 10.1126/science.3306916
  41. 10.1016/0014-4886(89)90029-0
  42. 10.1126/science.2321006
  43. 10.1016/0896-6273(90)90089-X
  44. 10.1016/0306-4522(92)90292-A
  45. 10.1016/0896-6273(89)90276-6
  46. 10.1083/jcb.117.3.629
  47. {'key': 'e_1_2_2_48_1', 'volume-title': 'Neuromethods, Volume 25. Animal Models of Neurological Disorders. Neurotrophic Factors', 'author': 'Persson H.', 'year': '1993'} / Neuromethods, Volume 25. Animal Models of Neurological Disorders. Neurotrophic Factors by Persson H. (1993)
  48. 10.1126/science.2154035
  49. 10.1126/science.1688328
  50. 10.1016/0896-6273(90)90203-R
  51. 10.1016/0896-6273(92)90183-E
  52. 10.1073/pnas.81.24.7951
  53. 10.1073/pnas.83.8.2714
  54. 10.1016/0166-2236(91)90097-E
  55. 10.1016/0014-4886(90)90068-4
  56. 10.1073/pnas.83.3.817
  57. 10.1002/j.1460-2075.1990.tb07564.x
  58. 10.1073/pnas.88.22.10037
Dates
Type When
Created 19 years, 4 months ago (April 7, 2006, 9:04 p.m.)
Deposited 1 year, 10 months ago (Oct. 25, 2023, 8:43 a.m.)
Indexed 1 month, 4 weeks ago (July 7, 2025, 2:02 a.m.)
Issued 32 years, 3 months ago (June 1, 1993)
Published 32 years, 3 months ago (June 1, 1993)
Published Online 19 years, 4 months ago (April 7, 2006)
Published Print 32 years, 3 months ago (June 1, 1993)
Funders 0

None

@article{Timmusk_1993, title={Widespread and Developmentally Regulated Expression of Neurotrophin‐4 mRNA in Rat Brain and Peripheral Tissues}, volume={5}, ISSN={1460-9568}, url={http://dx.doi.org/10.1111/j.1460-9568.1993.tb00526.x}, DOI={10.1111/j.1460-9568.1993.tb00526.x}, number={6}, journal={European Journal of Neuroscience}, publisher={Wiley}, author={Timmusk, Tõnis and Belluardo, Natale and Metsis, Madis and Persson, Håkan}, year={1993}, month=jun, pages={605–613} }