GFI1 functions to repress neuronal gene expression in the developing inner ear hair cells

Maggie S. Matern, Beatrice Milon, Erika L. Lipford, Mark McMurray, Yoko Ogawa, Andrew Tkaczuk, Yang Song, Ran Elkon, Ronna Hertzano

Research output: Contribution to journalArticlepeer-review

Abstract

Despite the known importance of the transcription factors ATOH1, POU4F3 and GFI1 in hair cell development and regeneration, their downstream transcriptional cascades in the inner ear remain largely unknown. Here, we have used Gfi1cre;RiboTag mice to evaluate changes to the hair cell translatome in the absence of GFI1. We identify a systematic downregulation of hair cell differentiation genes, concomitant with robust upregulation of neuronal genes in the GFI1-deficient hair cells. This includes increased expression of neuronal-associated transcription factors (e.g. Pou4f1) as well as transcription factors that serve dual roles in hair cell and neuronal development (e.g. Neurod1, Atoh1 and Insm1). We further show that the upregulated genes are consistent with the NEUROD1 regulon and are normally expressed in hair cells prior to GFI1 onset. Additionally, minimal overlap of differentially expressed genes in auditory and vestibular hair cells suggests that GFI1 serves different roles in these systems. From these data, we propose a dual mechanism for GFI1 in promoting hair cell development, consisting of repression of neuronal-associated genes as well as activation of hair cell-specific genes required for normal functional maturation.

Original languageEnglish
Article numberdev186015
JournalDevelopment (Cambridge)
Volume147
Issue number17
DOIs
StatePublished - Sep 2020

Keywords

  • GFI1
  • Hair cells
  • Inner ear

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