The role of Smad4 in vestibular development in mice.
The regulation of the bone morphogenetic protein (BMP) signal transduction pathway is important in the development of the inner ear and vestibular system. We reported previously that small mothers against decapentaplegic homolog-4 (Smad4) is required for inner ear cochlear development and normal auditory function in mammals; however, the distribution and functional mechanisms of Smad4 at various stages of vestibular development remained unclear. To investigate the relationship between the Smad4 gene and vestibular organ development, we measured changes in the expression of BMP4 and Smad4 during vestibular development in C57BL/6 mice. In addition, vestibular structures, pathologic changes, and the vestibular function of chondrocyte-specific Smad4 knockout mice were compared to those of the control group. We found that the expression of Smad4 in the inner ear was delayed compared with that of BMP4. Moreover, chondrocyte-specific Smad4 knockout homozygous mice showed stunted growth and partial vestibular deformities, but it showed less histologic changes in the vestibular end-organs and saccule dysfunction. These results suggest that Smad4 participates in late-stage shaping of the configuration of the vestibule and development of vestibular functional, but a Smad4-independent pathway for the inner ear vestibular BMP4 signal transduction could not be rule out.
Yang
Shi-ming
SM
Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, PR China. yangsm301@263.net
Deng
An-chun
AC
Huang
De-liang
DL
Sun
Jian-he
JH
Yang
Guan
G
Yu
Ya-ping
YP
Hou
Zhao-hui
ZH
Guo
Wei-wei
WW
Zhai
Suo-qiang
SQ
He
David Z Z
DZ
Han
Dong-yi
DY
Young
Wie-yen
WY
Yang
Xiao
X
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D005071:Evoked Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000502:physiology; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D014722:Vestibule, Labyrinth / Q000033:anatomy & histology* / Q000196:embryology* / Q000502:physiology*
D055415:Bone Morphogenetic Protein 4; D051901:Smad4 Protein; C490810:Smad4 protein, mouse