Abstract
The cochleo-vestibular ganglion (CVG) contains the neurons connecting the sensory epithelia of the inner ear to the cochlear and vestibular nuclei in the medulla. Expression of trkB protein-like immunoreactivity was studied in the developing CVG, using both Western blot and immunocytochemistry on tissue sections. Specific immunoreactivity was observed in the CVG from the 12th gestation day (gd) to the first postnatal week, reflecting the presence of high-affinity receptors for brain-derived neurotrophic factor (BDNF), a member of the NGF family of neurotrophins. Whole explants and dissociated cell cultures of cochlear (CG) and vestibular ganglion (VG) from mouse embryos and postnatal specimens were grown in neurotrophin-free medium to assay changes in neurite outgrowth and neuronal survival in response to the addition of physiological concentrations (0–5 ng/ml) of BDNF. Exogenous BDNF (2 ng/ml) promoted neurite outgrowth and neuronal survival in explants of both CG and VG, and the effects were stage-dependent. The onset of the response to BDNF occurred at gd 11–12. The response then reached a maximum between 14 and 18 gd and subsequently decreased, although it remained significantly present during the first postnatal week. BDNF-induced response was no longer observed in the mature cochlear and vestibular ganglion (after 30 postnatal days). The effects of BDNF on neuronal differentiation and survival were dose-dependent, starting at 0.5 ng/ml, with saturation at 2 ng/ml and half-maximal effect occurring between 1 and 1.5 ng/ml. On the basis of our results, we propose that BDNF may be physiologically involved in the control of both neuronal differentiation, and central and peripheral target-dependent neuronal death, in the CVG of embryos and early postnatal mice. BDNF may act alone or in cooperation with other neurotrophins to establish the afferent innervation of the inner ear sensory epithelium.
Similar content being viewed by others
References
Anniko M (1983) Embryonic development of vestibular sense organs and their innervation. In: Romand R (ed) Development of auditory and vestibular systems, vol 2. Elsevier, Amsterdam, pp 375–423
Ard MD, Morest DK (1984) Cell death during development of cochlear and vestibular ganglia of the chick. Int J Dev Neurosci 2:535–547
Ard MD, Morest DR, Hauger SH (1985) Trophic interactions between the cochleovestibular ganglion of the chick embryo and its synaptic targets in culture. Neuroscience 16:151–170
Avila MA, Varela-Nieto I, Romero G, Mato JM, Giraldez F, Van De Water TR, Represa J (1993) Brain-derived neurotrophic factor and neurotrophin-3 support the survival and neuritogenesis response of developing cochleovestibular ganglion neurons. Dev Biol 159:266–275
Barde YA (1989) Trophic factors and neuronal survival. Neuron 2:1525–1534
Berkemeier LR, Winslow JW, Kaplan DR, Nikolics K, Goeddel DV, Rosenthal A (1991) Neurotrophin 5: a novel neurotrophic factor that activates trk and trkB. Neuron 7:857–866
Bernd P, Represa J (1989) Characterization and localization of nerve growth factor receptors in the embryonic otic vesicle and cochleovestibular ganglion. Dev Biol 134:11–20
Bianchi LM, Cohan CS (1993) Effects of the neurotrophins and CNTF on developing statoacoustic neurons: Comparison with an otocyst-derived factor. Dev Biol 159:353–365
D'Amico-Martel A, Noden DM (1983) Contributions of placodal and neural crest cells to avian peripheral ganglia. Am J Anat 366:445–468
Davies AM, Thoenen H, Barde YA (1986) The response of chick sensory neurones to brain-derived neurotrophic factor. J Neurosci 6:1897–1903
Hallböök F, Ibańez CF, Persson H (1991) Evolutionary studies of the nerve growth factor reveal a novel member abundantly expressed in Xenopus ovary. Neuron 6:845–858
Hallböök F, Ibañez CF, Ebendal T, Persson H (1993) Cellular localization of brain-derived neurotrophic factor and neurotrophin-3 mesenger RNA expression in the early chicken embryo. Eur J Neurosci 1:1–14
Hemond SG, Morest DK (1992) Tropic effects of otic epithelium on chochleovestibular ganglion fibers growth in vitro. Anat Rec 232:273–284
Hempstead BL, Martin-Zanca D, Kaplan DR, Parada LF, Chao MV (1991) High affinity NGF binding requires coexpression of the trk protooncogene product and the low affinity NGF receptor. Nature 350:678–683
Heumann R, Korsching S, Scott J, Thoenen H (1984) Relationship between levels of nerve growth factor and its messenger RNA in the sympathetic ganglia and peripheral target tissues. EMBO J 3:3183–3189
Lefebvre PP, Leprince P, Weber T, Rigo JM, Delree P, Moonen G (1990) Neurotrophic effect of developing otic vesicle on cochleo-vestibular neurones: evidence for nerve growth factor involvement. Brain Res 507:254–260
Lefebvre PP, Van de Water TR, Represa J, Liu W, Bernd P, Modlin S, Moonen G, Mayer MB (1991) 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 (Stockh) 111:304–311
Lumsden AGS, Davies AM (1986) Chemotropic effect of specific target epithelium in the developing mammalian nervous system. Nature 323:538–539
McCarthy KD, Partlow LM (1976) Preparation of neuronal and non-neuronal cultures of embryonic chick sympathetic ganglia: a new method based in differential cell adhesiveness and the formation of homotypic neuronal aggregates. Brain Res 114:391–414
Meakin OS, Shooter EM (1992) The nerve growth factor family of receptors. Trends Neurosci 15:323–331
Pirvola U, Palgi J, Ylikoski J, Lehtonen E, Arumae U, Saarma M (1992) Brain-derived neurotrophic factor and neurotrophin 3 mRNAs are expressed in the peripheral target fields of developing inner ear ganglia. Proc Natl Acad Sci USA 89:9915–9919
Ramón y Cajal S (1908) Terminación periférica del nervio acustico de las aves. Trab Inst Cajal Invest Biol 6:161–176
Represa J, Bernd P (1989) Nerve growth factor and serum differentially regulate development of the embryonic otic vesicle and cochleovestibular ganglion in vitro. Dev Biol 134:21–29
Represa J, Avila MA, Miner C, Giraldez F, Romero G, Clemente R, Mato JM, Varela-Nieto I (1991a) Glycosyl-phosphatidylinositol/inositol phosphoglycan: a signalling system for the low affinity nerve growth factor receptor. Proc Natl Acad Sci USA 88:8016–8019
Represa J, Van de Water TR, Bernd P (1991b) Temporal pattern of nerve growth factor expression in developing cochlear and vestibular ganglia in quail and mouse. Anat Embryol 184:421–432
Represa J, Avila MA, Romero G, Mato JM, Giráldez F, Varela-Nieto I (1993) Brain-derived neurotrophic factor and neurotrophin-3 induce cell proliferation in the cochleovestibular ganglion through a glycosyl-phosphatidylinositol signalling system. Dev Biol 159:259–265
Rodriguez-Tebar A, Dechant G, Barde YA (1990) Binding of brain-derived neurotrophic factor to the nerve growth factor receptor. Neuron 4:487–492
Rodriguez-Tebar A, Dechant G, Grotz M, Barde YA (1992) Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor receptors and brain-derived neurotrophic factor. EMBO J 11:917–922
Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using Bicinchoninic Acid. Anal Biochem 150:76–85
Sobkowicz HM (1992) The development of innervation in the organ of Corti. In: Romand R (ed) Development of auditory and vestibular systems 2. Elsevier, Amsterdam, pp 59–95
Spoendlin H (1988) Neural anatomy of the inner ear. In: Jahn AF, Santos-Sachi J (eds) Physiology of the ear. Raven Press, New York, pp 201–219
Theiler K (1972) The house mouse. Development and normal stages from fertilization to 4 weeks of age. Springer, Berlin Heidelberg New York
Thoenen H (1991) The changing scene of neurotrophic factors. Trends Neurosci 14:165–170
Van De Water TR, Ruben RJ (1984) Neurotrophic interaction during in vitro development of the inner eara. Ann Otol Rhinol Laryngol 93:558–564
Van De Water TR, Frenz DA, Giraldez F, Represa J, Lefebvre PP, Rogister B, Moonen G (1992) Growth factors and development of the estato-acoustic system. In: Romand R (ed) Development of a auditory and vestibular systems 2. Elsevier, Amsterdam, pp 1–32
Von Bartheld CS, Patterson SL, Hener JG, Wheeler EF, Bothwell M, Rubel E (1991) Expression of nerve growth factor (NGF) receptors in the developing inner ear of chicken and rat. Development 113:455–470
Ylikoski J, Pirvola U, Moshnyakou M, Palgi J, Arumae U, Saarma M (1993) Expression patterns of neurotrophin and their receptor mRNAs in the rat inner ear. Hear Res 65:69–78
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vazquez, E., Van De Water, T.R., Del Valle, M. et al. Pattern of trkB protein-like immunoreactivity in vivo and the in vitro effects of brain-derived neurotrophic factor (BDNF) on developing cochlear and vestibular neurons. Anat Embryol 189, 157–167 (1994). https://doi.org/10.1007/BF00185774
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00185774