Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons
Summary: Neurons develop diverse synapses that vary in content, morphology, and size. Although transcriptional regulators of neurotransmitter identity are known, it remains unclear how synaptic features are patterned among neuronal subtypes. In the auditory system, glutamatergic synaptic properties...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725005674 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850136837765464064 |
|---|---|
| author | Isle Bastille Lucy Lee Cynthia Moncada-Reid Wei-Ming Yu Austen Sitko Andrea Yung Mina Zamani Nele Christophersen Reza Maroofian Hamid Galehdari Norbert Babai Barbara Vona Tobias Moser Lisa Goodrich |
| author_facet | Isle Bastille Lucy Lee Cynthia Moncada-Reid Wei-Ming Yu Austen Sitko Andrea Yung Mina Zamani Nele Christophersen Reza Maroofian Hamid Galehdari Norbert Babai Barbara Vona Tobias Moser Lisa Goodrich |
| author_sort | Isle Bastille |
| collection | DOAJ |
| description | Summary: Neurons develop diverse synapses that vary in content, morphology, and size. Although transcriptional regulators of neurotransmitter identity are known, it remains unclear how synaptic features are patterned among neuronal subtypes. In the auditory system, glutamatergic synaptic properties vary across three spiral ganglion neuron (SGN) subtypes that collectively encode sound. Here, we demonstrate that Maf transcription factors combinatorially shape synaptic properties in SGNs. SGN subtypes express different ratios of c-Maf and Mafb, which act redundantly to impart subtype identities and individually to shape subtype-appropriate gene expression programs. On their own, c-Maf and Mafb have independent and opposing effects on synaptic features and hearing. A mutation in the MAFB leucine zipper domain causes deafness in humans, underscoring the importance of regulated Maf activity for hearing. Thus, functional diversity and coordinated action of Maf family members enable flexible and robust control of gene expression needed to generate synaptic heterogeneity across neuronal subtypes. |
| format | Article |
| id | doaj-art-ca74d44ad9eb416a9d38952b0bcf3be2 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-ca74d44ad9eb416a9d38952b0bcf3be22025-08-20T02:31:00ZengElsevierCell Reports2211-12472025-06-0144611579610.1016/j.celrep.2025.115796Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neuronsIsle Bastille0Lucy Lee1Cynthia Moncada-Reid2Wei-Ming Yu3Austen Sitko4Andrea Yung5Mina Zamani6Nele Christophersen7Reza Maroofian8Hamid Galehdari9Norbert Babai10Barbara Vona11Tobias Moser12Lisa Goodrich13Department of Neurobiology, Harvard Medical School, Boston, MA, USADepartment of Neurobiology, Harvard Medical School, Boston, MA, USADepartment of Neurobiology, Harvard Medical School, Boston, MA, USADepartment of Neurobiology, Harvard Medical School, Boston, MA, USA; Department of Biology, Loyola University Chicago, Chicago, IL, USADepartment of Neurobiology, Harvard Medical School, Boston, MA, USADepartment of Neurobiology, Harvard Medical School, Boston, MA, USA; Genentech, South San Francisco, CA, USADepartment of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran; Narges Medical Genetics and Prenatal Diagnosis Laboratory, Kianpars, Ahvaz, Iran; Department of Neuromuscular Diseases, Queen Square, Institute of Neurology, University College London, London, UKInstitute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany; Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, GermanyDepartment of Neuromuscular Diseases, Queen Square, Institute of Neurology, University College London, London, UKDepartment of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, IranInstitute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, GermanyInstitute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany; Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, GermanyInstitute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, GermanyDepartment of Neurobiology, Harvard Medical School, Boston, MA, USA; Corresponding authorSummary: Neurons develop diverse synapses that vary in content, morphology, and size. Although transcriptional regulators of neurotransmitter identity are known, it remains unclear how synaptic features are patterned among neuronal subtypes. In the auditory system, glutamatergic synaptic properties vary across three spiral ganglion neuron (SGN) subtypes that collectively encode sound. Here, we demonstrate that Maf transcription factors combinatorially shape synaptic properties in SGNs. SGN subtypes express different ratios of c-Maf and Mafb, which act redundantly to impart subtype identities and individually to shape subtype-appropriate gene expression programs. On their own, c-Maf and Mafb have independent and opposing effects on synaptic features and hearing. A mutation in the MAFB leucine zipper domain causes deafness in humans, underscoring the importance of regulated Maf activity for hearing. Thus, functional diversity and coordinated action of Maf family members enable flexible and robust control of gene expression needed to generate synaptic heterogeneity across neuronal subtypes.http://www.sciencedirect.com/science/article/pii/S2211124725005674CP: Neuroscience |
| spellingShingle | Isle Bastille Lucy Lee Cynthia Moncada-Reid Wei-Ming Yu Austen Sitko Andrea Yung Mina Zamani Nele Christophersen Reza Maroofian Hamid Galehdari Norbert Babai Barbara Vona Tobias Moser Lisa Goodrich Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons Cell Reports CP: Neuroscience |
| title | Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons |
| title_full | Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons |
| title_fullStr | Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons |
| title_full_unstemmed | Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons |
| title_short | Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons |
| title_sort | combinatorial transcriptional regulation establishes subtype appropriate synaptic properties in auditory neurons |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725005674 |
| work_keys_str_mv | AT islebastille combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT lucylee combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT cynthiamoncadareid combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT weimingyu combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT austensitko combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT andreayung combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT minazamani combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT nelechristophersen combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT rezamaroofian combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT hamidgalehdari combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT norbertbabai combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT barbaravona combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT tobiasmoser combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons AT lisagoodrich combinatorialtranscriptionalregulationestablishessubtypeappropriatesynapticpropertiesinauditoryneurons |