Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development.
The neurally expressed genes Brn-3.1 and Brn-3.2 (refs 1-6) are mammalian orthologues of the Caenorhabditis elegans unc-86 gene that constitute, with Brn-3.0 (refs 1-3,8,9), the class IV POU-domain transcription factors. Brn-3.1 and Brn-3.2 provide a means of exploring the potentially distinct biological functions of expanded gene families in neural development. The highly related members of the Brn-3 family have similar DNA-binding preferences and overlapping expression patterns in the sensory nervous system, midbrain and hindbrain, suggesting functional redundancy. Here we report that Brn-3.1 and Brn-3.2 critically modulate the terminal differentiation of distinct sensorineural cells in which they exhibit selective spatial and temporal expression patterns. Deletion of the Brn-3.2 gene causes the loss of most retinal ganglion cells, defining distinct ganglion cell populations. Mutation of Brn-3.1 results in complete deafness, owing to a failure of hair cells to appear in the inner ear, with subsequent loss of cochlear and vestibular ganglia.
Erkman
L
L
Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, La Jolla 92093, USA.
McEvilly
R J
RJ
Luo
L
L
Ryan
A K
AK
Hooshmand
F
F
O'Connell
S M
SM
Keithley
E M
EM
Rapaport
D H
DH
Ryan
A F
AF
Rosenfeld
M G
MG
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D003638:Deafness / Q000196:embryology / Q000235:genetics; D007758:Ear, Inner / Q000196:embryology*; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology*; D005123:Eye / Q000196:embryology*; D017353:Gene Deletion; D006198:Hair Cells, Auditory / Q000002:abnormalities / Q000196:embryology; D018398:Homeodomain Proteins; D017403:In Situ Hybridization; D051379:Mice; D005810:Multigene Family; D012160:Retina / Q000196:embryology; D012165:Retinal Ganglion Cells / Q000166:cytology; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C085559:Pou4f2 protein, mouse; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors