CHANGES IN THE SUBCELLULAR-LOCALIZATION OF THE BRN4 GENE-PRODUCT PRECEDE MESENCHYMAL REMODELING OF THE OTIC CAPSULE

To better understand the genetic mechanisms that regulate the formatio n of the temporal bone, we have characterized the developmental expres sion pattern of the mouse gene, Brn4/Pou3f4, which plays a central rol e in bony labyrinth formation. Expression of this gene is initially de tected in the ventral aspect of the otic capsule at 10.5 days post coi tus (dpc), and correlates with the onset of mesenchymal condensation i n the oric capsule. As the otic capsule condenses further and surround s the entire otic vesicle, the Brn4 gene product is detected throughou t the inner ear in the mesenchyme of both the cochlear and vestibular aspects. Early in otic embryogenesis, the Brn4 gene product is localiz ed to the nucleus of the vast majority of cells in which it is express ed. The Brn4 gene product remains nuclear in those regions of the otic capsule that eventually give rise to the mature bony labyrinth. Howev er, the subcellular localization of the Brn4 gene product shifts from strictly nuclear to perinuclear in those regions of the otic capsule t hat will cavitate to form acellular regions in the temporal bone, such as the scala tympani, scala vestibuli, and the internal auditory meat us. These data provide a detailed analysis of the expression pattern o f the Brn4 gene, and provide insight into the role of the Brn4 gene pr oduct and its regulation during otic capsule formation. (C) 1998 Publi shed by Elsevier Science B.V. All rights reserved.