Abstract
In situ hybridization was used to study the site and timing of the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 5 (NT-5) mRNAs in the developing inner ear of the rat. In the sensory epithelia, the levels of NGF and NT-5 mRNAs were below the detection limit. NT-3 and BDNF mRNAs were expressed in the otic vesicle in overlapping but also in distinct regions. Later in development, NT-3 transcripts were localized to the differentiating sensory and supporting cells of the auditory organ and vestibular maculae. In these sensory epithelia, the intensity of NT-3 mRNA expression decreased in parallel with maturation. The expression of BDNF mRNA was restricted to the sensory cells of both the auditory and vestibular organs, including ampullary cristae. In bioassays, BDNF and NT-3, but not NGF, at physiological concentrations induced neurite outgrowth from the statoacoustic ganglion explants. These results demonstrate that NT-3 and BDNF, rather than NGF and NT-5, are the primary neurotrophins present in the target fields of the cochlear and vestibular neurons. Expression of NT-3 and BDNF mRNAs in the otic vesicle before and during the ingrowth of neurites from the statoacoustic ganglion suggests that NT-3 or BDNF or both may serve as chemoattractants for the early nerve fibers. The results also suggest that these neurotrophins have a role in later development of the cochlear and vestibular neurons.
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- Abe H., Wataya H., Amano O., Kondo H. Localization of nerve growth factor receptor in developing inner ear of rats. Acta Otolaryngol. 1991;111(4):691–698. doi: 10.3109/00016489109138401. [DOI] [PubMed] [Google Scholar]
- Ard M. D., Morest D. K., Hauger S. H. Trophic interactions between the cochleovestibular ganglion of the chick embryo and its synaptic targets in culture. Neuroscience. 1985 Sep;16(1):151–170. doi: 10.1016/0306-4522(85)90053-3. [DOI] [PubMed] [Google Scholar]
- Ayer-LeLievre C., Olson L., Ebendal T., Hallbök F., Persson H. Nerve growth factor mRNA and protein in the testis and epididymis of mouse and rat. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2628–2632. doi: 10.1073/pnas.85.8.2628. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Barde Y. A. Trophic factors and neuronal survival. Neuron. 1989 Jun;2(6):1525–1534. doi: 10.1016/0896-6273(89)90040-8. [DOI] [PubMed] [Google Scholar]
- 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]
- Bernd P., Represa J. Characterization and localization of nerve growth factor receptors in the embryonic otic vesicle and cochleovestibular ganglion. Dev Biol. 1989 Jul;134(1):11–20. doi: 10.1016/0012-1606(89)90073-0. [DOI] [PubMed] [Google Scholar]
- D'Amico-Martel A., Noden D. M. Contributions of placodal and neural crest cells to avian cranial peripheral ganglia. Am J Anat. 1983 Apr;166(4):445–468. doi: 10.1002/aja.1001660406. [DOI] [PubMed] [Google Scholar]
- Davies A. M., Bandtlow C., Heumann R., Korsching S., Rohrer H., Thoenen H. Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. 1987 Mar 26-Apr 1Nature. 326(6111):353–358. doi: 10.1038/326353a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Ernfors P., Wetmore C., Olson L., Persson H. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family. Neuron. 1990 Oct;5(4):511–526. doi: 10.1016/0896-6273(90)90090-3. [DOI] [PubMed] [Google Scholar]
- Hallbök F., Ayer-Lelièvre C., Ebendal T., Persson H. Expression of nerve growth factor receptor mRNA during early development of the chicken embryo: emphasis on cranial ganglia. Development. 1990 Apr;108(4):693–704. doi: 10.1242/dev.108.4.693. [DOI] [PubMed] [Google Scholar]
- 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]
- Hempstead B. L., Martin-Zanca D., Kaplan D. R., Parada L. F., Chao M. V. High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature. 1991 Apr 25;350(6320):678–683. doi: 10.1038/350678a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Klein R., Jing S. Q., Nanduri V., O'Rourke E., Barbacid M. The trk proto-oncogene encodes a receptor for nerve growth factor. Cell. 1991 Apr 5;65(1):189–197. doi: 10.1016/0092-8674(91)90419-y. [DOI] [PubMed] [Google Scholar]
- Klein R., Nanduri V., Jing S. A., Lamballe F., Tapley P., Bryant S., Cordon-Cardo C., Jones K. R., Reichardt L. F., Barbacid M. The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell. 1991 Jul 26;66(2):395–403. doi: 10.1016/0092-8674(91)90628-c. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lamballe F., Klein R., Barbacid M. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell. 1991 Sep 6;66(5):967–979. doi: 10.1016/0092-8674(91)90442-2. [DOI] [PubMed] [Google Scholar]
- Lefebvre P. P., Leprince P., Weber T., Rigo J. M., Delree P., Moonen G. Neuronotrophic effect of developing otic vesicle on cochleo-vestibular neurons: evidence for nerve growth factor involvement. Brain Res. 1990 Jan 22;507(2):254–260. doi: 10.1016/0006-8993(90)90279-k. [DOI] [PubMed] [Google Scholar]
- Lefebvre P. P., Van de Water T. R., Represa J., Liu W., Bernd P., Modlin S., Moonen G., Mayer M. B. Temporal pattern of nerve growth factor (NGF) binding in vivo and the in vitro effects of NGF on cultures of developing auditory and vestibular neurons. Acta Otolaryngol. 1991;111(2):304–311. doi: 10.3109/00016489109137392. [DOI] [PubMed] [Google Scholar]
- 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]
- Lenoir M., Shnerson A., Pujol R. Cochlear receptor development in the rat with emphasis on synaptogenesis. Anat Embryol (Berl) 1980;160(3):253–262. doi: 10.1007/BF00305106. [DOI] [PubMed] [Google Scholar]
- Levi-Montalcini R. The nerve growth factor: thirty-five years later. EMBO J. 1987 May;6(5):1145–1154. doi: 10.1002/j.1460-2075.1987.tb02347.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindsay R. M., Thoenen H., Barde Y. A. Placode and neural crest-derived sensory neurons are responsive at early developmental stages to brain-derived neurotrophic factor. Dev Biol. 1985 Dec;112(2):319–328. doi: 10.1016/0012-1606(85)90402-6. [DOI] [PubMed] [Google Scholar]
- Lumsden A. G., Davies A. M. Earliest sensory nerve fibres are guided to peripheral targets by attractants other than nerve growth factor. Nature. 1983 Dec 22;306(5945):786–788. doi: 10.1038/306786a0. [DOI] [PubMed] [Google Scholar]
- Maisonpierre P. C., Belluscio L., Squinto S., Ip N. Y., Furth M. E., Lindsay R. M., Yancopoulos G. D. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990 Mar 23;247(4949 Pt 1):1446–1451. doi: 10.1126/science.247.4949.1446. [DOI] [PubMed] [Google Scholar]
- Otten U., Ehrhard P., Peck R. Nerve growth factor induces growth and differentiation of human B lymphocytes. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10059–10063. doi: 10.1073/pnas.86.24.10059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pirvola U., Lehtonen E., Ylikoski J. Spatiotemporal development of cochlear innervation and hair cell differentiation in the rat. Hear Res. 1991 Apr;52(2):345–355. doi: 10.1016/0378-5955(91)90024-4. [DOI] [PubMed] [Google Scholar]
- Raivich G., Zimmermann A., Sutter A. Nerve growth factor (NGF) receptor expression in chicken cranial development. J Comp Neurol. 1987 Feb 8;256(2):229–245. doi: 10.1002/cne.902560204. [DOI] [PubMed] [Google Scholar]
- Represa J., Bernd P. Nerve growth factor and serum differentially regulate development of the embryonic otic vesicle and cochleovestibular ganglion in vitro. Dev Biol. 1989 Jul;134(1):21–29. doi: 10.1016/0012-1606(89)90074-2. [DOI] [PubMed] [Google Scholar]
- Represa J., Van de Water T. R., Bernd P. Temporal pattern of nerve growth factor receptor expression in developing cochlear and vestibular ganglia in quail and mouse. Anat Embryol (Berl) 1991;184(5):421–432. doi: 10.1007/BF01236048. [DOI] [PubMed] [Google Scholar]
- Rodriguez-Tébar A., Dechant G., Barde Y. A. Binding of brain-derived neurotrophic factor to the nerve growth factor receptor. Neuron. 1990 Apr;4(4):487–492. doi: 10.1016/0896-6273(90)90107-q. [DOI] [PubMed] [Google Scholar]
- 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]
- Soppet D., Escandon E., Maragos J., Middlemas D. S., Reid S. W., Blair J., Burton L. E., Stanton B. R., Kaplan D. R., Hunter T. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell. 1991 May 31;65(5):895–903. doi: 10.1016/0092-8674(91)90396-g. [DOI] [PubMed] [Google Scholar]
- Squinto S. P., Stitt T. N., Aldrich T. H., Davis S., Bianco S. M., Radziejewski C., Glass D. J., Masiakowski P., Furth M. E., Valenzuela D. M. trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Cell. 1991 May 31;65(5):885–893. doi: 10.1016/0092-8674(91)90395-F. [DOI] [PubMed] [Google Scholar]
- Van de Water T. R. Tissue interactions and cell differentiation: neurone-sensory cell interaction during otic development. Development. 1988;103 (Suppl):185–193. doi: 10.1242/dev.103.Supplement.185. [DOI] [PubMed] [Google Scholar]
- Whittemore S. R., Friedman P. L., Larhammar D., Persson H., Gonzalez-Carvajal M., Holets V. R. Rat beta-nerve growth factor sequence and site of synthesis in the adult hippocampus. J Neurosci Res. 1988 Aug;20(4):403–410. doi: 10.1002/jnr.490200402. [DOI] [PubMed] [Google Scholar]
- von Bartheld C. S., Patterson S. L., Heuer J. G., Wheeler E. F., Bothwell M., Rubel E. W. Expression of nerve growth factor (NGF) receptors in the developing inner ear of chick and rat. Development. 1991 Oct;113(2):455–470. doi: 10.1242/dev.113.2.455. [DOI] [PubMed] [Google Scholar]