TY - JOUR
T1 - NGF, BDNF and NT-3 play unique roles in the in vitro development and patterning of innervation of the mammalian inner ear
AU - Staecker, Hinrich
AU - Van De Water, Thomas R.
AU - Lefebvre, Philippe P.
AU - Liu, Wei
AU - Moghadassi, Masseih
AU - Galinovic-Schwartz, Vera
AU - Malgrange, Brigitte
AU - Moonen, Gustave
PY - 1996/3/29
Y1 - 1996/3/29
N2 - Developing cochleovestibular ganglion (CVG) neurons depend upon interaction with the otocyst, their peripheral target tissue, for both trophic support and tropic guidance. RT-PCR of E11 through E14 otocyst-CVG RNA extracts have shown that NGF as well as BDNF and NT-3 are expressed in the developing inner ear (in situ RT-PCR on tissue sections of E12 otocysts localized all three neurotrophins to the otocyst). To evaluate the functional significance of NGF, BDNF and NT-3 expression, E10.5 otocyst-CVG explants were treated with antisense oligonucleotides and compared to sense treated and control cultures. Confocal microscopic analysis revealed that treatment with BDNF antisense resulted in extensive neuronal cell death, downregulation of NGF caused an inhibition of neuritogenesis and a decrease in the neuronal population of the CVG, whereas treatment with NT-3 antisense resulted in a loss of target directed CVG neuritic ingrowth in this in vitro model. The effect of NGF or BDNF antisense treatment could be prevented by the simultaneous addition of the respective growth factor. These findings demonstrate that each of the three neurotrophins have important roles during the onset of neuritic ingrowth of the CVG neurons to the otocyst.
AB - Developing cochleovestibular ganglion (CVG) neurons depend upon interaction with the otocyst, their peripheral target tissue, for both trophic support and tropic guidance. RT-PCR of E11 through E14 otocyst-CVG RNA extracts have shown that NGF as well as BDNF and NT-3 are expressed in the developing inner ear (in situ RT-PCR on tissue sections of E12 otocysts localized all three neurotrophins to the otocyst). To evaluate the functional significance of NGF, BDNF and NT-3 expression, E10.5 otocyst-CVG explants were treated with antisense oligonucleotides and compared to sense treated and control cultures. Confocal microscopic analysis revealed that treatment with BDNF antisense resulted in extensive neuronal cell death, downregulation of NGF caused an inhibition of neuritogenesis and a decrease in the neuronal population of the CVG, whereas treatment with NT-3 antisense resulted in a loss of target directed CVG neuritic ingrowth in this in vitro model. The effect of NGF or BDNF antisense treatment could be prevented by the simultaneous addition of the respective growth factor. These findings demonstrate that each of the three neurotrophins have important roles during the onset of neuritic ingrowth of the CVG neurons to the otocyst.
KW - Antisense oligonucleotide
KW - Cochleovestibular ganglion
KW - In vitro
KW - Neurite guidance
KW - Neuritogenesis
KW - Neuronal survival
KW - Neurotrophin
KW - Otocyst
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UR - http://www.scopus.com/inward/citedby.url?scp=0029864159&partnerID=8YFLogxK
U2 - 10.1016/0165-3806(95)00198-0
DO - 10.1016/0165-3806(95)00198-0
M3 - Article
C2 - 8861722
AN - SCOPUS:0029864159
VL - 92
SP - 49
EP - 60
JO - Developmental Brain Research
JF - Developmental Brain Research
SN - 0165-3806
IS - 1
ER -