Authors
Bastille I, Lee L, Moncada-Reid C, Yu WM, Sitko A, Yung A, Zamani M, Christophersen N, Maroofian R, Galehdari H, Babai N, Vona B, Moser T, Goodrich L
Journal
Cell Reports
Citation
Cell Rep 2025. accepted manuscript.
Abstract
Neurons develop diverse synapses that vary in content, morphology, and size. Although transcriptional regulators of neurotransmitter identity have been identified, it remains unclear how synaptic features are patterned among neuronal subtypes. In the auditory system, glutamatergic synaptic properties vary across three subtypes of spiral ganglion neurons (SGNs) that collectively encode sound information. Here, we demonstrate that Maf transcription factors act combinatorially to shape synaptic heterogeneity in SGNs. SGN subtypes express different ratios of c-Maf and Mafb, which act redundantly to impart subtype identities and also individually to shape subtype-appropriate programs of gene expression. Indeed, on their own, c-Maf and Mafb have independent and opposing effects on synaptic features and how SGNs respond to sound. A mutation in the MAFB leucine zipper domain causes deafness in humans, underscoring the importance of properly regulated Maf activity for hearing. Thus, functional diversity and coordinated action of Maf family members enables flexible and robust control of gene expression needed to generate synaptic heterogeneity across neuronal subtypes.
DOI
No DOI available.
