TY - JOUR
T1 - Requirement for Lmo4 in the vestibular morphogenesis of mouse inner ear
AU - Deng, Min
AU - Pan, Ling
AU - Xie, Xiaoling
AU - Gan, Lin
N1 - Funding Information:
We thank Dr. Alexandra Joyner for W4 mouse ES cells, Drs. James Martin, Terence H. Rabbitts, Hirohide Takebayashi, and Doris Wu for providing the in situ hybridization probes for Bmp4, Lmo4, Lmx1a and Lfng , Drs. Amy Kiernan and Richard Libby for critical reading of this manuscript and valuable comments, and the members of the Gan Laboratory for technical assistance. This work was supported by NIH grant DC008856 to L.G. and the Research to Prevent Blindness challenge grant to the Department of Ophthalmology at the University of Rochester.
PY - 2010/2/1
Y1 - 2010/2/1
N2 - During development, compartmentalization of an early embryonic structure produces blocks of cells with distinct properties and developmental potentials. The auditory and vestibular components of vertebrate inner ears are derived from defined compartments within the otocyst during embryogenesis. The vestibular apparatus, including three semicircular canals, saccule, utricle, and their associated sensory organs, detects angular and linear acceleration of the head and relays the information through vestibular neurons to vestibular nuclei in the brainstem. How the early developmental events manifest vestibular structures at the molecular level is largely unknown. Here, we show that LMO4, a LIM-domain-only transcriptional regulator, is required for the formation of semicircular canals and their associated sensory cristae. Targeted disruption of Lmo4 resulted in the dysmorphogenesis of the vestibule and in the absence of three semicircular canals, anterior and posterior cristae. In Lmo4-null otocysts, canal outpouches failed to form and cell proliferation was reduced in the dorsolateral region. Expression analysis of the known otic markers showed that Lmo4 is essential for the normal expression of Bmp4, Fgf10, Msx1, Isl1, Gata3, and Dlx5 in the dorsolateral domain of the otocyst, whereas the initial compartmentalization of the otocyst remains unaffected. Our results demonstrate that Lmo4 controls the development of the dorsolateral otocyst into semicircular canals and cristae through two distinct mechanisms: regulating the expression of otic specific genes and stimulating the proliferation of the dorsolateral part of the otocyst.
AB - During development, compartmentalization of an early embryonic structure produces blocks of cells with distinct properties and developmental potentials. The auditory and vestibular components of vertebrate inner ears are derived from defined compartments within the otocyst during embryogenesis. The vestibular apparatus, including three semicircular canals, saccule, utricle, and their associated sensory organs, detects angular and linear acceleration of the head and relays the information through vestibular neurons to vestibular nuclei in the brainstem. How the early developmental events manifest vestibular structures at the molecular level is largely unknown. Here, we show that LMO4, a LIM-domain-only transcriptional regulator, is required for the formation of semicircular canals and their associated sensory cristae. Targeted disruption of Lmo4 resulted in the dysmorphogenesis of the vestibule and in the absence of three semicircular canals, anterior and posterior cristae. In Lmo4-null otocysts, canal outpouches failed to form and cell proliferation was reduced in the dorsolateral region. Expression analysis of the known otic markers showed that Lmo4 is essential for the normal expression of Bmp4, Fgf10, Msx1, Isl1, Gata3, and Dlx5 in the dorsolateral domain of the otocyst, whereas the initial compartmentalization of the otocyst remains unaffected. Our results demonstrate that Lmo4 controls the development of the dorsolateral otocyst into semicircular canals and cristae through two distinct mechanisms: regulating the expression of otic specific genes and stimulating the proliferation of the dorsolateral part of the otocyst.
KW - Inner ear development
KW - LIM
KW - LMO
KW - LMO4
KW - Otic vesicle
KW - Otocyst
KW - Transcription factor
KW - Vestibular morphogenesis
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U2 - 10.1016/j.ydbio.2009.11.003
DO - 10.1016/j.ydbio.2009.11.003
M3 - Article
C2 - 19913004
AN - SCOPUS:73549116094
SN - 0012-1606
VL - 338
SP - 38
EP - 49
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -