Bone morphogenetic protein 4 promotes the survival and preserves the structure of flow-sorted Bhlhb5+ cochlear spiral ganglion neurons in vitro

Abstract SGNs are the primary auditory neurons, and damage or loss of SGNs leads to sensorineural hearing loss. BMP4 is a growth factor that belongs to the TGF-β superfamily and has been shown to play a key role during development, but little is known about its effect on postnatal cochlear SGNs in m...

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Autores principales: Muhammad Waqas, Shan Sun, Chuanyin Xuan, Qiaojun Fang, Xiaoli Zhang, Irum-us Islam, Jieyu Qi, Shasha Zhang, Xia Gao, Mingliang Tang, Haibo Shi, Huawei Li, Renjie Chai
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/a48764753ef04360a476c81629882cc4
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spelling oai:doaj.org-article:a48764753ef04360a476c81629882cc42021-12-02T16:06:03ZBone morphogenetic protein 4 promotes the survival and preserves the structure of flow-sorted Bhlhb5+ cochlear spiral ganglion neurons in vitro10.1038/s41598-017-03810-w2045-2322https://doaj.org/article/a48764753ef04360a476c81629882cc42017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03810-whttps://doaj.org/toc/2045-2322Abstract SGNs are the primary auditory neurons, and damage or loss of SGNs leads to sensorineural hearing loss. BMP4 is a growth factor that belongs to the TGF-β superfamily and has been shown to play a key role during development, but little is known about its effect on postnatal cochlear SGNs in mice. In this study, we used the P3 Bhlhb5-cre/tdTomato transgenic mouse model and FACS to isolate a pure population of Bhlhb5+ SGNs. We found that BMP4 significantly promoted SGN survival after 7 days of culture. We observed fewer apoptotic cells and decreased expression of pro-apoptotic marker genes after BMP4 treatment. We also found that BMP4 promoted monopolar neurite outgrowth of isolated SGNs, and high concentrations of BMP4 preserved the number and the length of neurites in the explant culture of the modiolus harboring the SGNs. We showed that high concentration of BMP4 enhanced neurite growth as determined by the higher average number of filopodia and the larger area of the growth cone. Finally, we found that high concentrations of BMP4 significantly elevated the synapse density of SGNs in explant culture. Thus, our findings suggest that BMP4 has the potential to promote the survival and preserve the structure of SGNs.Muhammad WaqasShan SunChuanyin XuanQiaojun FangXiaoli ZhangIrum-us IslamJieyu QiShasha ZhangXia GaoMingliang TangHaibo ShiHuawei LiRenjie ChaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Muhammad Waqas
Shan Sun
Chuanyin Xuan
Qiaojun Fang
Xiaoli Zhang
Irum-us Islam
Jieyu Qi
Shasha Zhang
Xia Gao
Mingliang Tang
Haibo Shi
Huawei Li
Renjie Chai
Bone morphogenetic protein 4 promotes the survival and preserves the structure of flow-sorted Bhlhb5+ cochlear spiral ganglion neurons in vitro
description Abstract SGNs are the primary auditory neurons, and damage or loss of SGNs leads to sensorineural hearing loss. BMP4 is a growth factor that belongs to the TGF-β superfamily and has been shown to play a key role during development, but little is known about its effect on postnatal cochlear SGNs in mice. In this study, we used the P3 Bhlhb5-cre/tdTomato transgenic mouse model and FACS to isolate a pure population of Bhlhb5+ SGNs. We found that BMP4 significantly promoted SGN survival after 7 days of culture. We observed fewer apoptotic cells and decreased expression of pro-apoptotic marker genes after BMP4 treatment. We also found that BMP4 promoted monopolar neurite outgrowth of isolated SGNs, and high concentrations of BMP4 preserved the number and the length of neurites in the explant culture of the modiolus harboring the SGNs. We showed that high concentration of BMP4 enhanced neurite growth as determined by the higher average number of filopodia and the larger area of the growth cone. Finally, we found that high concentrations of BMP4 significantly elevated the synapse density of SGNs in explant culture. Thus, our findings suggest that BMP4 has the potential to promote the survival and preserve the structure of SGNs.
format article
author Muhammad Waqas
Shan Sun
Chuanyin Xuan
Qiaojun Fang
Xiaoli Zhang
Irum-us Islam
Jieyu Qi
Shasha Zhang
Xia Gao
Mingliang Tang
Haibo Shi
Huawei Li
Renjie Chai
author_facet Muhammad Waqas
Shan Sun
Chuanyin Xuan
Qiaojun Fang
Xiaoli Zhang
Irum-us Islam
Jieyu Qi
Shasha Zhang
Xia Gao
Mingliang Tang
Haibo Shi
Huawei Li
Renjie Chai
author_sort Muhammad Waqas
title Bone morphogenetic protein 4 promotes the survival and preserves the structure of flow-sorted Bhlhb5+ cochlear spiral ganglion neurons in vitro
title_short Bone morphogenetic protein 4 promotes the survival and preserves the structure of flow-sorted Bhlhb5+ cochlear spiral ganglion neurons in vitro
title_full Bone morphogenetic protein 4 promotes the survival and preserves the structure of flow-sorted Bhlhb5+ cochlear spiral ganglion neurons in vitro
title_fullStr Bone morphogenetic protein 4 promotes the survival and preserves the structure of flow-sorted Bhlhb5+ cochlear spiral ganglion neurons in vitro
title_full_unstemmed Bone morphogenetic protein 4 promotes the survival and preserves the structure of flow-sorted Bhlhb5+ cochlear spiral ganglion neurons in vitro
title_sort bone morphogenetic protein 4 promotes the survival and preserves the structure of flow-sorted bhlhb5+ cochlear spiral ganglion neurons in vitro
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/a48764753ef04360a476c81629882cc4
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