title: CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice.
abstract: Chemotactic cytokines (chemokines) are a highly conserved class of secreted signaling molecules that are important in various cellular processes. CXC chemokine ligand 12 (CXCL12) and its receptor, CXC chemokine receptor 4 (CXCR4) have been previously reported to be crucial for the establishment of neural networks in different neuronal systems. However, it is unclear whether the CXCL12/CXCR4 signaling pathway regulates the development of the cochlea. The current study investigated the effects of the CXCL12/CXCR4 signaling pathway on cochlear development in neonatal mice. The expression levels of CXCL12 and CXCR4 were detected using immunofluorescence, reverse transcription‑quantitative polymerase chain reaction and western blot analysis demonstrating that CXCL12 and CXCR4 expression were significantly increased during cochlear development in neonatal mice. Treatment of spiral ganglion neurons with CXCL12 significantly decreased the protein expression levels of caspase‑3 and cleaved caspase‑3, indicating that CXCL12/CXCR4 signaling increased cell survival of spiral ganglion neurons. Furthermore, CXCL12 treatment significantly increased the number and length of neurites extending from spiral ganglion neurons. By contrast, the in vitro effects of CXCL12 were significantly abrogated by AMD100, a CXCR4 antagonist. Additionally, inhibiting CXCL12/CXCR4 signaling in neonatal mice significantly reduced the cell number and altered the morphology of spiral ganglion neurons in vivo. Thus, the present study indicates that the CXCL12/CXCR4 signaling pathway is important during the development of cochleae in neonatal mice.
authors.affiliation: Department of Otolaryngology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, Xi'an XD Group Hospital, Xi'an, Shaanxi 710077, P.R. China.
authors.forename: Ji-Zhou
authors.initials: JZ
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yue
authors.affiliation: Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000096:biosynthesis; D054377:Chemokine CXCL12 / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D016501:Neurites / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology*; D013136:Spiral Ganglion / Q000166:cytology / Q000254:growth & development*
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; C505409:Casp3 protein, mouse; D053148:Caspase 3