| First Author | Du J | Year | 2018 |
| Journal | Mol Med Rep | Volume | 17 |
| Issue | 2 | Pages | 2357-2365 |
| PubMed ID | 29207144 | Mgi Jnum | J:319916 |
| Mgi Id | MGI:6863571 | Doi | 10.3892/mmr.2017.8115 |
| Citation | Du J, et al. (2018) DNER modulates the length, polarity and synaptogenesis of spiral ganglion neurons via the Notch signaling pathway. Mol Med Rep 17(2):2357-2365 |
| abstractText | The Delta/Notchlike epidermal growth factorrelated receptor (DNER) serves an important role in the developing central nervous system. However, the actions of DNER in the development of the spiral ganglion in the inner ear have yet to be elucidated. Wildtype C57BL/6 mice were housed and timemated for use in the present study. Primary neuronal cultures were prepared using spiral ganglion progenitors isolated from the modiolus of postnatal day 1 (P1) mice. DNER recombinant lentiviral vectors were constructed and transfected into the cultured primary neurons. The relative proportion of differentiated neurons and the length of their neurites were evaluated using microscopy. The results of the present study demonstrated that DNER was expressed in spiral ganglion neurons (SGNs) that exhibited significant polarity in the early differentiation stages; DNER expression gradually decreased until the polarity was lost on week 35. The in vitro expression of DNER was revealed to be similar to that in vivo. When DNER expression was silenced using RNA interference, the polarity of the differentiated neurons was altered and they exhibited significantly reduced dendritic length. In addition, the proportion of bipolar neurons was decreased compared with the control group. Furthermore, the expression of alphasynuclein and the GluR2/3 subunits of the alphaamino3hydroxy5methyl4-isoxazolepropionic acid glutamate receptor were also reduced in cultured neurons in which DNER was silenced. Notch1 was coexpressed with DNER in SGNs isolated from P1 mice. The indirect Notch inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]Sphenylglycine tbutyl ester also affected the polarity and the formation of protrusions, and reduced the expression of DNER and glial fibrillary acidic protein in SGNs. In conclusion, the present study demonstrated that DNER was expressed in SGNs and appeared to be involved in the mechanisms underlying neuronal polarity and neuritogenesis, via a Notchdependent signaling pathway. |
