Different types of spiral ganglion neurons (SGNs) are essential for auditory perception by transmitting complex auditory information from hair cells (HCs) to the brain. Here, we use deep, single cell transcriptomics to study the molecular mechanisms that govern their identity and organization in mice. We identify a core set of temporally patterned genes and gene regulatory networks that may contribute to the diversification of SGNs through sequential binary decisions and demonstrate a role for NEUROD1 in driving specification of a Ic-SGN phenotype. We also find that each trajectory of the decision tree is defined by initial co-expression of alternative subtype molecular controls followed by gradual shifts toward cell fate resolution. Finally, analysis of both developing SGN and HC types reveals cell-cell signaling potentially playing a role in the differentiation of SGNs. Our results indicate that SGN identities are drafted prior to birth and reveal molecular principles that shape their differentiation and will facilitate studies of their development, physiology, and dysfunction.

Department of Neuroimmunology Center for Brain Research Medical University Vienna 1090 Vienna Austria

Department of Neuroscience Karolinska Institutet Stockholm Sweden

Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden

Institute of Biotechnology CAS 25250 Vestec Czech Republic

Ming Wai Lau Centre for Reparative Medicine Stockholm Node Karolinska Institutet Stockholm Sweden

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Harmony in the Molecular Orchestra of Hearing: Developmental Mechanisms from the Ear to the Brain

ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization