RT Journal Article
SR Electronic
T1 Gata3 Is a Critical Regulator of Cochlear Wiring
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3679
OP 3691
DO 10.1523/JNEUROSCI.4703-12.2013
VO 33
IS 8
A1 Jessica M. Appler
A1 Cindy C. Lu
A1 Noah R. Druckenbrod
A1 Wei-Ming Yu
A1 Edmund J. Koundakjian
A1 Lisa V. Goodrich
YR 2013
UL http://www.jneurosci.org/content/33/8/3679.abstract
AB 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 which Gata3 is 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 using in vitro neurite 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.