Reciprocal negative regulation between Lmx1a and Lmo4 is required for inner ear formation

Yanhan Huang, Jennifer Hill, Andrew Yatteau, Loksum Wong, Tao Jiang, Jelena Petrovic, Lin Gan, Lijin Dong, Doris K. Wu

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

LIM-domain containing transcription factors (LIM-TFs) are conserved factors important for embryogenesis. The specificity of these factors in transcriptional regulation is conferred by the complexes that they form with other proteins such as LIM-domain-binding (Ldb) proteins and LIM-domain only (LMO) proteins. Unlike LIM-TFs, these proteins do not bind DNA directly. LMO proteins are negative regulators of LIM-TFs and function by competing with LIM-TFs for binding to Ldb’s. Although the LIM-TF Lmx1a is expressed in the developing mouse hindbrain, which provides many of the extrinsic signals for inner ear formation, conditional knock-out embryos of both sexes show that the inner ear source of Lmx1a is the major contributor of ear patterning. In addition, we have found that the reciprocal interaction between Lmx1a and Lmo4 (a LMO protein within the inner ear) mediates the formation of both vestibular and auditory structures. Lmo4 negatively regulates Lmx1a to form the three sensory cristae, the anterior semicircular canal, and the shape of the utricle in the vestibule. Furthermore, this negative regulation blocks ectopic sensory formation in the cochlea. In contrast, Lmx1a negatively regulates Lmo4 in mediating epithelial resorption of the canal pouch, which gives rise to the anterior and posterior semicircular canals. We also found that Lmx1a is independently required for the formation of the endolymphatic duct and hair cells in the basal cochlear region.

Original languageEnglish (US)
Pages (from-to)5429-5440
Number of pages12
JournalJournal of Neuroscience
Volume38
Issue number23
DOIs
StatePublished - Jun 6 2018
Externally publishedYes

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Keywords

  • Cochlea
  • Cristae
  • Development
  • Genetics
  • Inner ear
  • Semicircular canals

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Huang, Y., Hill, J., Yatteau, A., Wong, L., Jiang, T., Petrovic, J., Gan, L., Dong, L., & Wu, D. K. (2018). Reciprocal negative regulation between Lmx1a and Lmo4 is required for inner ear formation. Journal of Neuroscience, 38(23), 5429-5440. https://doi.org/10.1523/JNEUROSCI.2484-17.2018