المؤلفون: Francesc Palau, Belén Mollá, Federico V. Pallardo, Pilar Gonzalez-Cabo, Diana C. Muñoz-Lasso, Pablo Calap-Quintana, José Luis García-Giménez

المساهمون: Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Fundación Ramón Areces, Generalitat Valenciana, Centro de Investigación Biomédica en Red Enfermedades Raras (España)

المصدر: Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
Scientific Reports
Digital.CSIC. Repositorio Institucional del CSIC
instname

مصطلحات موضوعية: Cofilin 1, Ataxia, Science, Phosphatase, Growth Cones, Mutation, Missense, macromolecular substances, Immunofluorescence, Molecular neuroscience, Filamentous actin, Article, Actin-Related Protein 2-3 Complex, Mice, Mice, Neurologic Mutants, Phosphoserine, Ganglia, Spinal, Iron-Binding Proteins, medicine, Neurites, Phosphoprotein Phosphatases, Animals, Phosphorylation, Actin, Cells, Cultured, Peripheral neuropathies, Neurons, Multidisciplinary, biology, medicine.diagnostic_test, Microfilament Proteins, Cofilin, Actin cytoskeleton, Actins, Axons, Cell biology, Actin Cytoskeleton, Disease Models, Animal, nervous system, Friedreich Ataxia, Frataxin, biology.protein, Medicine, medicine.symptom, Protein Processing, Post-Translational

الوصف: 10 páginas, 3 figuras. Contiene material suplementario accesible en: https://doi.org/10.1038/s41598-020-62050-7Test
Abnormalities in actin cytoskeleton have been linked to Friedreich's ataxia (FRDA), an inherited peripheral neuropathy characterised by an early loss of neurons in dorsal root ganglia (DRG) among other clinical symptoms. Despite all efforts to date, we still do not fully understand the molecular events that contribute to the lack of sensory neurons in FRDA. We studied the adult neuronal growth cone (GC) at the cellular and molecular level to decipher the connection between frataxin and actin cytoskeleton in DRG neurons of the well-characterised YG8R Friedreich's ataxia mouse model. Immunofluorescence studies in primary cultures of DRG from YG8R mice showed neurons with fewer and smaller GCs than controls, associated with an inhibition of neurite growth. In frataxin-deficient neurons, we also observed an increase in the filamentous (F)-actin/monomeric (G)-actin ratio (F/G-actin ratio) in axons and GCs linked to dysregulation of two crucial modulators of filamentous actin turnover, cofilin-1 and the actin-related protein (ARP) 2/3 complex. We show how the activation of cofilin is due to the increase in chronophin (CIN), a cofilin-activating phosphatase. Thus cofilin emerges, for the first time, as a link between frataxin deficiency and actin cytoskeleton alterations.
Tis work was supported by grants from the Ministerio de Economía y Competitividad de España [Grant no. PI11/00678; SAF2015-66625-R] within the framework of the National R+ D+ I Plan and co-funded by the Instituto de Salud Carlos III (ISCIII)-Subdirección General de Evaluación y Fomento de la Investigación and FEDER funds; Fundación Ramón Areces (CIVP18A3899); the Generalitat Valenciana (ACOMP/2014/058; PROMETEO/2018/135). CIBERER is an initiative developed by the Instituto de Salud Carlos III in cooperative and translational research on rare diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b0bf079744afed55d0942ff17d57f4b7Test
https://doaj.orgTest/article/1c2e1b48290849ff8db4190d1f6da79c

المؤلفون: Dionicio Siegel, Evguenia Ivakhnitskaia, Matthew R Chin, Victor H. Guaiquil

المصدر: Scientific Reports
Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)

مصطلحات موضوعية: 0301 basic medicine, Nervous system, Cell type, Cell biology, Science, Neurogenesis, Xanthones, Growth Cones, Biology, Axonal growth cone, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, In vivo, Ganglia, Spinal, medicine, Animals, Trigeminal Nerve, IC50, Neurons, Multidisciplinary, Regeneration (biology), SEMA3A, Semaphorin-3A, Embryonic stem cell, 030104 developmental biology, medicine.anatomical_structure, Medicine, 030217 neurology & neurosurgery, Neuroscience, Signal Transduction

الوصف: Semaphorin3A is considered a classical repellent molecule for developing neurons and a potent inhibitor of regeneration after nervous system trauma. Vinaxanthone and other Sema3A inhibitors are currently being tested as possible therapeutics to promote nervous system regeneration from injury. Our previous study on Sema3A demonstrated a switch in Sema3A’s function toward induction of nerve regeneration in adult murine corneas and in culture of adult peripheral neurons. The aim of the current study is to determine the direct effects of Vinaxanthone on the Sema3A induced adult neuronal growth. We first demonstrate that Vinaxanthone maintains its anti-Sema3A activity in embryonic dorsal root ganglia neurons by inhibiting Sema3A-induced growth cone collapse. However, at concentrations approximating its IC50 Vinaxanthone treatment does not significantly inhibit neurite formation of adult peripheral neurons induced by Sema3A treatment. Furthermore, Vinaxanthone has off target effects when used at concentrations above its IC50, and inhibits neurite growth of adult neurons treated with either Sema3A or NGF. Our results suggest that Vinaxanthone’s pro-regenerative effects seen in multiple in vivo models of neuronal injury in adult animals need further investigation due to the pleiotropic effect of Sema3A on various non-neuronal cell types and the possible effect of Vinaxanthone on other neuroregenerative signals.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e27ca1d65980b9adf423d9990837ae0aTest
http://europepmc.org/articles/PMC8217491Test

المؤلفون: Barbato, Sara, Marrocco, Elena, Intartaglia, Daniela, Pizzo, Mariateresa, Asteriti, Sabrina, Naso, Federica, Falanga, Danila, Bhat, Rajeshwari S., Meola, Nicola, Carissimo, Annamaria, Karali, Marianthi, Prosser, Haydn M., Cangiano, Lorenzo, Surace, Enrico Maria, Banfi, Sandro, Conte, Ivan, CONTE, IVAN

المساهمون: Intartaglia, Daniela [0000-0001-5256-3188], Asteriti, Sabrina [0000-0003-2846-9305], Cangiano, Lorenzo [0000-0001-7145-1288], Banfi, Sandro [0000-0002-6541-8833], Apollo - University of Cambridge Repository, Barbato, Sara, Marrocco, Elena, Intartaglia, Daniela, Pizzo, Mariateresa, Asteriti, Sabrina, Naso, Federica, Falanga, Danila, Bhat, Rajeshwari S, Meola, Nicola, Carissimo, Annamaria, Karali, Marianthi, Prosser, Haydn M, Cangiano, Lorenzo, Surace, Enrico Maria, Banfi, Sandro, Conte, Ivan, Bhat, Rajeshwari S., Prosser, Haydn M.

المصدر: Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
Barbato, S, Marrocco, E, Intartaglia, D, Pizzo, M, Asteriti, S, Naso, F, Falanga, D, Bhat, R S, Meola, N, Carissimo, A, Karali, M, Prosser, H M, Cangiano, L, Surace, E M, Banfi, S & Conte, I 2017, ' MiR-211 is essential for adult cone photoreceptor maintenance and visual function ', Scientific Reports, vol. 7, no. 1, 17004 . https://doi.org/10.1038/s41598-017-17331-zTest
Scientific Reports

مصطلحات موضوعية: 0301 basic medicine, Male, retina, genetic structures, degeneration, lcsh:Medicine, Biology, Retinal Cone Photoreceptor Cells, Article, Transcriptome, 03 medical and health sciences, Mice, rods, cones, Cone dystrophy, microRNA, retina, rods, cones, miRNAs, mouse, degeneration, disease, medicine, Animals, Cone Dystrophy, Eye Proteins, lcsh:Science, mouse, Vision, Ocular, Regulation of gene expression, Mice, Knockout, disease, Retina, Multidisciplinary, Gene Expression Profiling, lcsh:R, medicine.disease, Cell biology, Gene expression profiling, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, miRNAs, Female, lcsh:Q, sense organs, Function (biology)

الوصف: MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that play an important role in the control of fundamental biological processes in both physiological and pathological conditions. Their function in retinal cells is just beginning to be elucidated, and a few have been found to play a role in photoreceptor maintenance and function. MiR-211 is one of the most abundant miRNAs in the developing and adult eye. However, its role in controlling vertebrate visual system development, maintenance and function so far remain incompletely unexplored. Here, by targeted inactivation in a mouse model, we identify a critical role of miR-211 in cone photoreceptor function and survival. MiR-211 knockout (−/−) mice exhibited a progressive cone dystrophy accompanied by significant alterations in visual function. Transcriptome analysis of the retina from miR-211−/− mice during cone degeneration revealed significant alteration of pathways related to cell metabolism. Collectively, this study highlights for the first time the impact of miR-211 function in the retina and significantly contributes to unravelling the role of specific miRNAs in cone photoreceptor function and survival.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd98bf355c31e3bd92d26425118d862fTest
http://link.springer.comTest/article/10.1038/s41598-017-17331-z

المؤلفون: Louis-Philippe Croteau, Tzu Jen Kao, Artur Kania

المصدر: Scientific Reports
Scientific Reports, Vol 9, Iss 1, Pp 1-17 (2019)

مصطلحات موضوعية: 0301 basic medicine, animal structures, Science, Growth Cones, Article, Cell membrane, 03 medical and health sciences, 0302 clinical medicine, Developmental biology, Netrin, medicine, Animals, Ephrin, Axon, Growth cone, Receptor, 030304 developmental biology, Motor Neurons, 0303 health sciences, Multidisciplinary, Axon and dendritic guidance, Chemistry, fungi, Membrane Proteins, Netrin-1, Ephrin-A5, Axons, Axon Guidance, Cell biology, 030104 developmental biology, medicine.anatomical_structure, nervous system, Proteolysis, embryonic structures, Medicine, Axon guidance, Ephrin A5, sense organs, Chickens, 030217 neurology & neurosurgery

الوصف: Axonal growth cones are guided by molecular cues in the extracellular environment. The mechanisms of combinatorial integration of guidance signals at the growth cone cell membrane are still being unravelled. Limb-innervating axons of vertebrate spinal lateral motor column (LMC) neurons are attracted to netrin-1 via its receptor, Neogenin, and are repelled from ephrin-A5 through its receptor EphA4. The presence of both cues elicits synergistic guidance of LMC axons, but the mechanism of this effect remains unknown. Using fluorescence immunohistochemistry, we show that ephrin-A5 increases LMC growth cone Neogenin protein levels and netrin-1 binding. This effect is enhanced by overexpressing EphA4 and is inhibited by blocking ephrin-A5-EphA4 binding. These effects have a functional consequence on LMC growth cone responses since bath addition of ephrin-A5 increases the responsiveness of LMC axons to netrin-1. Surprisingly, the overexpression of EphA4 lacking its cytoplasmic tail, also enhances Neogenin levels at the growth cone and potentiates LMC axon preference for growth on netrin-1. Since netrins and ephrins participate in a wide variety of biological processes, the enhancement of netrin-1 signalling by ephrins may have broad implications.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cbdcce1d25825d5f520f4497f21fea2fTest
https://doi.org/10.1038/s41598-019-48519-0Test

المؤلفون: Kotaro Oka, R. Suzuki, Kohji Hotta

المصدر: Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
Scientific Reports

مصطلحات موضوعية: 0301 basic medicine, Growth Cones, lcsh:Medicine, Mitochondrion, Mitochondrial Size, Axonal Transport, Mitochondrial Dynamics, Article, 03 medical and health sciences, Adenosine Triphosphate, Ganglia, Spinal, Animals, Inner membrane, Premovement neuronal activity, Rats, Wistar, Inner mitochondrial membrane, lcsh:Science, Cells, Cultured, Membrane Potential, Mitochondrial, Neurons, Membrane potential, Multidisciplinary, Chemistry, lcsh:R, Axons, Mitochondria, Rats, 030104 developmental biology, Mitochondrial Membranes, Biophysics, Axoplasmic transport, Mitochondrial fission, lcsh:Q, sense organs, Signal Transduction

الوصف: The importance of highly active mitochondria and their contribution to neuronal function has been of recent interest. In most cases, however, mitochondrial activity is estimated using measurements of mitochondrial inner membrane potential (IMPmito), and little is known about the dynamics of native mitochondrial ATP (ATPmito). This study conducted simultaneous imaging of IMPmito and ATPmito in neurons to explore their behaviour and their correlation during physiological mitochondrial/neuronal activity. We found that mitochondrial size, transport velocity and transport direction are not dependent on ATPmito or IMPmito. However, changes in ATPmito and IMPmito during mitochondrial fission/fusion were found; IMPmito depolarized via mitochondrial fission and hyperpolarized via fusion, and ATPmito levels increased after fusion. Because the density of mitochondria is higher in growth cones (GCs) than in axonal processes, integrated ATPmito signals (density × ATPmito) were higher in GCs. This integrated signal in GCs correlated with axonal elongation. However, while the averaged IMPmito was relatively hyperpolarized in GCs, there was no correlation between IMPmito in GCs and axonal elongation. A detailed time-course analysis performed to clarify the reason for these discrepancies showed that IMPmito and ATPmito levels did not always correlate accurately; rather, there were several correlation patterns that changed over time.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4590030260d0da7732d7c86e4cabed40Test
http://link.springer.comTest/article/10.1038/s41598-018-21109-2

المؤلفون: Robin Scharrenberg, Birgit Schwanke, Durga Praveen Meka, Michael R. Kreutz, Oliver Kobler, Sabine Windhorst, Froylan Calderon de Anda, Bing Zhao, Theresa König, Marina Mikhaylova

المصدر: Scientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
Scientific Reports
Scientific reports, 7:9583

مصطلحات موضوعية: 0301 basic medicine, Neurite, Cell polarity, Cellular neuroscience, Growth Cones, lcsh:Medicine, macromolecular substances, Biology, Filamentous actin, Microtubules, Article, 03 medical and health sciences, Mice, Microtubule, Pregnancy, Animals, Growth cone, lcsh:Science, Microtubule nucleation, Neurons, Multidisciplinary, Axon extension, Neuropeptides, lcsh:R, Cell Polarity, Immunohistochemistry, Actins, Axons, Cell biology, Rats, 030104 developmental biology, Treadmilling, Female, lcsh:Q, Biomarkers, Protein Binding

الوصف: Neuronal polarization is reflected by different dynamics of microtubule and filamentous actin (F-actin). Axonal microtubules are more stable than those in the remaining neurites, while dynamics of F-actin in axonal growth cones clearly exceed those in their dendritic counterparts. However, whether a functional interplay exists between the microtubule network and F-actin dynamics in growing axons and whether this interplay is instrumental for breaking cellular symmetry is currently unknown. Here, we show that an increment on microtubule stability or number of microtubules is associated with increased F-actin dynamics. Moreover, we show that Drebrin E, an F-actin and microtubule plus-end binding protein, mediates this cross talk. Drebrin E segregates preferentially to growth cones with a higher F-actin treadmilling rate, where more microtubule plus-ends are found. Interruption of the interaction of Drebrin E with microtubules decreases F-actin dynamics and arrests neuronal polarization. Collectively the data show that microtubules modulate F-actin dynamics for initial axon extension during neuronal development.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::22f705a7e5e52e2035c0329b826da366Test
http://link.springer.comTest/article/10.1038/s41598-017-09832-8

المؤلفون: Jee-Yin Ahn, Inwoo Hwang, Kye Won Park, Jeong-Yun Choi, Byeong-Seong Kim, Sung-Woo Cho, Hyo Rim Ko, Eun-Ju Jin

المصدر: Scientific Reports
Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)

مصطلحات موضوعية: 0301 basic medicine, Proteasome Endopeptidase Complex, Neurite, Moesin, Science, Neurogenesis, Growth Cones, Neuronal Outgrowth, macromolecular substances, Filamentous actin, PC12 Cells, Article, 03 medical and health sciences, Mice, Radixin, Animals, Humans, Phosphorylation, Growth cone, Protein kinase B, Multidisciplinary, 030102 biochemistry & molecular biology, Chemistry, Protein Stability, Membrane Proteins, Actins, Cell biology, Rats, Cytoskeletal Proteins, 030104 developmental biology, HEK293 Cells, Proteolysis, Medicine, Signal transduction, Proto-Oncogene Proteins c-akt, Protein Binding, Signal Transduction

الوصف: Neurite growth is controlled by a complex molecular signaling network that regulates filamentous actin (F-actin) dynamics at the growth cone. The evolutionarily conserved ezrin, radixin, and moesin family of proteins tether F-actin to the cell membrane when phosphorylated at a conserved threonine residue and modulate neurite outgrowth. Here we show that Akt binds to and phosphorylates a threonine 573 residue on radixin. Akt-mediated phosphorylation protects radixin from ubiquitin-dependent proteasomal degradation, thereby enhancing radixin protein stability, which permits proper neurite outgrowth and growth cone formation. Conversely, the inhibition of Akt kinase or disruption of Akt-dependent phosphorylation reduces the binding affinity of radixin to F-actin as well as lowers radixin protein levels, resulting in decreased neurite outgrowth and growth cone formation. Our findings suggest that Akt signaling regulates neurite outgrowth by stabilizing radixin interactions with F-actin, thus facilitating local F-actin dynamics.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::832ca8e43b83f2d44bac9bce8bee9f26Test
http://europepmc.org/articles/PMC5803261Test

المؤلفون: Alessandra Ghigo, Elena Parmigiani, Alessandro Vercelli, Marina Boido, Luca Murru, Luisa Ponzoni, Alessandro Umbach, Donatella Garzotto, Alessandro Mauro, Gaia Berto, Maria Passafaro, Emilio Hirsch, Giorgio R. Merlo, Lorenzo Priano, Valentina Zamboni, Nadia El-Assawy, Ferdinando Dicunto, Maria Armentano, Elisa Ciraolo

المصدر: Scientific Reports
Scientific Reports, Vol 8, Iss 1, Pp 1-16 (2018)

مصطلحات موضوعية: 0301 basic medicine, rac1 GTP-Binding Protein, Science, Growth Cones, Regulator, Hyperphosphorylation, RAC1, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Loss of Function Mutation, Neurites, Animals, Phosphorylation, Growth cone, Multidisciplinary, Chemistry, Pyramidal Cells, GTPase-Activating Proteins, Neuropeptides, Dendrites, Cofilin, Actin cytoskeleton, Actins, Axons, Cell biology, 030104 developmental biology, Medicine, Signal transduction, 030217 neurology & neurosurgery, Signal Transduction

الوصف: The small-GTPase Rac1 is a key molecular regulator linking extracellular signals to actin cytoskeleton dynamics. Loss-of-function mutations in RAC1 and other genes of the Rac signaling pathway have been implicated in the pathogenesis of Intellectual Disability (ID). The Rac1 activity is negatively controlled by GAP proteins, however the effect of Rac1 hyperactivity on neuronal networking in vivo has been poorly studied. ArhGAP15 is a Rac-specific negative regulator, expressed in the main subtypes of pyramidal cortical neurons. In the absence of ArhGAP15, cortical pyramidal neurons show defective neuritogenesis, delayed axonal elongation, reduced dendritic branching, both in vitro and in vivo. These phenotypes are associated with altered actin dynamics at the growth cone due to increased activity of the PAK-LIMK pathway and hyperphosphorylation of ADF/cofilin. These results can be explained by shootin1 hypo-phosphorylation and uncoupling with the adhesion system. Functionally, ArhGAP15−/− mice exhibit decreased synaptic density, altered electroencephalographic rhythms and cognitive deficits. These data suggest that both hypo- and hyperactivation of the Rac pathway due to mutations in Rac1 regulators can result in conditions of ID, and that a tight regulation of Rac1 activity is required to attain the full complexity of the cortical networks.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3f7b23c37ad7cb25aae141dbb8bcac4fTest
https://pubmed.ncbi.nlm.nih.gov/29740022Test

المؤلفون: Henri C. Jimbo, Shigeyuki Oba, Tatsuya Yamada, Makoto Nishiyama, Kazushi Ikeda, Yuichi Sakumura, Kyonsoo Hong, Shin Ishii

المصدر: Scientific Reports
Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)

مصطلحات موضوعية: 0301 basic medicine, Xenopus, Growth Cones, lcsh:Medicine, Article, Membrane Potentials, 03 medical and health sciences, Extracellular, Animals, Protein kinase A, Growth cone, lcsh:Science, Cyclic GMP, Membrane potential, Multidisciplinary, biology, Chemistry, lcsh:R, Computational Biology, Bayes Theorem, Models, Theoretical, biology.organism_classification, Electrophysiology, 030104 developmental biology, Chloride channel, lcsh:Q, Biological system, Intracellular

الوصف: Biological cells express intracellular biomolecular information to the extracellular environment as various physical responses. We show a novel computational approach to estimate intracellular biomolecular pathways from growth cone electrophysiological responses. Previously, it was shown that cGMP signaling regulates membrane potential (MP) shifts that control the growth cone turning direction during neuronal development. We present here an integrated deterministic mathematical model and Bayesian reversed-engineering framework that enables estimation of the molecular signaling pathway from electrical recordings and considers both the system uncertainty and cell-to-cell variability. Our computational method selects the most plausible molecular pathway from multiple candidates while satisfying model simplicity and considering all possible parameter ranges. The model quantitatively reproduces MP shifts depending on cGMP levels and MP variability potential in different experimental conditions. Lastly, our model predicts that chloride channel inhibition by cGMP-dependent protein kinase (PKG) is essential in the core system for regulation of the MP shifts.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::153d69bd74e2425c0b5b38c353c1273dTest
https://pubmed.ncbi.nlm.nih.gov/29540815Test

المؤلفون: Shan Sun, Xia Gao, Irum-us Islam, Jieyu Qi, Qiaojun Fang, Huawei Li, Shasha Zhang, Renjie Chai, Chuanyin Xuan, Muhammad Waqas, Haibo Shi, Xiaoli Zhang, Mingliang Tang

المصدر: Scientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
Scientific Reports

مصطلحات موضوعية: 0301 basic medicine, Pathology, medicine.medical_specialty, animal structures, Neurite, Cell Survival, Science, medicine.medical_treatment, Growth Cones, Neuronal Outgrowth, Population, Apoptosis, Mice, Transgenic, Bone Morphogenetic Protein 4, In Vitro Techniques, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Basic Helix-Loop-Helix Transcription Factors, otorhinolaryngologic diseases, medicine, Animals, education, Growth cone, Cells, Cultured, Spiral ganglion, Neurons, education.field_of_study, Multidisciplinary, Growth factor, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Bone morphogenetic protein 4, Synapses, embryonic structures, Medicine, sense organs, Spiral Ganglion, Filopodia, 030217 neurology & neurosurgery, Explant culture

الوصف: 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.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c5538d5b920802c2d5c80e5a5e52d801Test
https://doi.org/10.1038/s41598-017-03810-wTest