Conditional deletion of N-Myc disrupts neurosensory and non-sensory development of the ear

Benjamin Kopecky, Peter Santi, Shane Johnson, Heather Schmitz, Bernd Fritzsch

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Ear development requires interactions of transcription factors for proliferation and differentiation. The proto-oncogene N-Myc is a member of the Myc family that regulates proliferation. To investigate the function of N-Myc, we conditionally knocked out N-Myc in the ear using Tg(Pax2-Cre) and Foxg1KiCre. N-Myc CKOs had reduced growth of the ear, abnormal morphology including fused sensory epithelia, disrupted histology, and disorganized neuronal innervation. Using Thin-Sheet Laser Imaging Microscopy (TSLIM), 3D reconstruction and quantification of the cochlea revealed a greater than 50% size reduction. Immunochemistry and in situ hybridization showed a gravistatic organ-cochlear fusion and a "circularized" apex with no clear inner and outer hair cells. Furthermore, the abnormally developed cochlea had cross innervation from the vestibular ganglion near the basal tip. These findings are put in the context of the possible functional relationship of N-Myc with a number of other cell proliferative and fate determining genes during ear development.

Original languageEnglish (US)
Pages (from-to)1373-1390
Number of pages18
JournalDevelopmental Dynamics
Volume240
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • Cell cycle
  • Histogenesis
  • Inner ear
  • Morphogenesis
  • N-Myc

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