A Gata3–Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing
Information flow through neural circuits is determined by the nature of the synapses linking the subtypes of neurons. How neurons acquire features distinct to each synapse remains unknown. We show that the transcription factor Mafb drives the formation of auditory ribbon synapses, which are speciali...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2013-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/01341 |
| _version_ | 1818018965234909184 |
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| author | Wei-Ming Yu Jessica M Appler Ye-Hyun Kim Allison M Nishitani Jeffrey R Holt Lisa V Goodrich |
| author_facet | Wei-Ming Yu Jessica M Appler Ye-Hyun Kim Allison M Nishitani Jeffrey R Holt Lisa V Goodrich |
| author_sort | Wei-Ming Yu |
| collection | DOAJ |
| description | Information flow through neural circuits is determined by the nature of the synapses linking the subtypes of neurons. How neurons acquire features distinct to each synapse remains unknown. We show that the transcription factor Mafb drives the formation of auditory ribbon synapses, which are specialized for rapid transmission from hair cells to spiral ganglion neurons (SGNs). Mafb acts in SGNs to drive differentiation of the large postsynaptic density (PSD) characteristic of the ribbon synapse. In Mafb mutant mice, SGNs fail to develop normal PSDs, leading to reduced synapse number and impaired auditory responses. Conversely, increased Mafb accelerates synaptogenesis. Moreover, Mafb is responsible for executing one branch of the SGN differentiation program orchestrated by the Gata3 transcriptional network. Remarkably, restoration of Mafb rescues the synapse defect in Gata3 mutants. Hence, Mafb is a powerful regulator of cell-type specific features of auditory synaptogenesis that offers a new entry point for treating hearing loss. |
| first_indexed | 2024-04-14T07:46:39Z |
| format | Article |
| id | doaj.art-f133127fccd145e8ae3c48a4be418387 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:46:39Z |
| publishDate | 2013-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f133127fccd145e8ae3c48a4be4183872022-12-22T02:05:19ZengeLife Sciences Publications LtdeLife2050-084X2013-12-01210.7554/eLife.01341A Gata3–Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearingWei-Ming Yu0Jessica M Appler1Ye-Hyun Kim2Allison M Nishitani3Jeffrey R Holt4Lisa V Goodrich5Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Otolaryngology and FM Kirby Neurobiology Center, Children’s Hospital Boston, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Otolaryngology and FM Kirby Neurobiology Center, Children’s Hospital Boston, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesInformation flow through neural circuits is determined by the nature of the synapses linking the subtypes of neurons. How neurons acquire features distinct to each synapse remains unknown. We show that the transcription factor Mafb drives the formation of auditory ribbon synapses, which are specialized for rapid transmission from hair cells to spiral ganglion neurons (SGNs). Mafb acts in SGNs to drive differentiation of the large postsynaptic density (PSD) characteristic of the ribbon synapse. In Mafb mutant mice, SGNs fail to develop normal PSDs, leading to reduced synapse number and impaired auditory responses. Conversely, increased Mafb accelerates synaptogenesis. Moreover, Mafb is responsible for executing one branch of the SGN differentiation program orchestrated by the Gata3 transcriptional network. Remarkably, restoration of Mafb rescues the synapse defect in Gata3 mutants. Hence, Mafb is a powerful regulator of cell-type specific features of auditory synaptogenesis that offers a new entry point for treating hearing loss.https://elifesciences.org/articles/01341auditoryspiral ganglion neuronribbon synapseMafbGata3synaptogenesi |
| spellingShingle | Wei-Ming Yu Jessica M Appler Ye-Hyun Kim Allison M Nishitani Jeffrey R Holt Lisa V Goodrich A Gata3–Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing eLife auditory spiral ganglion neuron ribbon synapse Mafb Gata3 synaptogenesi |
| title | A Gata3–Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing |
| title_full | A Gata3–Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing |
| title_fullStr | A Gata3–Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing |
| title_full_unstemmed | A Gata3–Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing |
| title_short | A Gata3–Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing |
| title_sort | gata3 mafb transcriptional network directs post synaptic differentiation in synapses specialized for hearing |
| topic | auditory spiral ganglion neuron ribbon synapse Mafb Gata3 synaptogenesi |
| url | https://elifesciences.org/articles/01341 |
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