Gata3 Is a Critical Regulator of Cochlear Wiring
| Autor: | Lisa V. Goodrich, Wei-Ming Yu, Jessica M. Appler, Cindy C. Lu, Noah R. Druckenbrod, Edmund J. Koundakjian |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Neurite Neurogenesis Regulator Sensory system GATA3 Transcription Factor Biology Article Mice otorhinolaryngologic diseases medicine Animals Transcription factor Cochlea Spiral ganglion Mice Knockout General Neuroscience Cell Differentiation Embryonic stem cell Gene expression profiling medicine.anatomical_structure Animals Newborn Female sense organs Spiral Ganglion Neuroscience |
| Zdroj: | The Journal of Neuroscience. 33:3679-3691 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | Spiral ganglion neurons (SGNs) play a key role in hearing by rapidly and faithfully transmitting signals from the cochlea to the brain. Identification of the transcriptional networks that ensure the proper specification and wiring of SGNs during development will lay the foundation for efforts to rewire a damaged cochlea. Here, we show that the transcription factor Gata3, which is expressed in SGNs throughout their development, is essential for formation of the intricately patterned connections in the cochlea. We generated conditional knock-out mice in whichGata3is deleted after SGNs are specified. Cochlear wiring is severely disrupted in these animals, with premature extension of neurites that follow highly abnormal trajectories toward their targets, as shown usingin vitroneurite outgrowth assays together with time-lapse imaging of whole embryonic cochleae. Expression profiling of mutant neurons revealed a broad shift in gene expression toward a more differentiated state, concomitant with minor changes in SGN identity. Thus, Gata3 appears to serve as an “intermediate regulator” that guides SGNs through differentiation and preserves the auditory fate. As the first auditory-specific regulator of SGN development, Gata3 provides a useful molecular entry point for efforts to engineer SGNs for the restoration of hearing. |
| Databáze: | OpenAIRE |
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