The fully linked HTML version of this article has now been published.
Development ePress online publication date 24 Dec 2003
doi: 10.1242/dev.00943
Research article
Six1 controls patterning of the mouse otic vesicle
Hidenori Ozaki,
Kazuaki Nakamura,
Jun-ichi Funahashi,
Keiko Ikeda,
Gen Yamada,
Hisashi Tokano,
Hiro-oki Okamura,
Ken Kitamura,
Shigeaki Muto,
Hayato Kotaki,
Katsuko Sudo,
Reiko Horai,
Yoichiro Iwakura,
and
Kiyoshi Kawakami*
* Author for correspondence (e-mail: kkawakam{at}jichi.ac.jp)
Six1 is a member of the Six family homeobox genes, which function as components of the Pax-Six-Eya-Dach gene network to control organ development. Six1 is expressed in otic vesicles, nasal epithelia, branchial arches/pouches, nephrogenic cords, somites and a limited set of ganglia. In this study, we established Six1-deficient mice and found that development of the inner ear, nose, thymus, kidney and skeletal muscle was severely affected. Six1-deficient embryos were devoid of inner ear structures, including cochlea and vestibule, while their endolymphatic sac was enlarged. The inner ear anomaly began at around E10.5 and Six1 was expressed in the ventral region of the otic vesicle in the wild-type embryos at this stage. In the otic vesicle of Six1-deficient embryos, expressions of Otx1, Otx2, Lfng and Fgf3, which were expressed ventrally in the wild-type otic vesicles, were abolished, while the expression domains of Dlx5, Hmx3, Dach1 and Dach2, which were expressed dorsally in the wild-type otic vesicles, expanded ventrally. Our results indicate that Six1 functions as a key regulator of otic vesicle patterning at early embryogenesis and controls the expression domains of downstream otic genes responsible for respective inner ear structures. In addition, cell proliferation was reduced and apoptotic cell death was enhanced in the ventral region of the otic vesicle, suggesting the involvement of Six1 in cell proliferation and survival. In spite of the similarity of otic phenotypes of Six1- and Shh-deficient mice, expressions of Six1 and Shh were mutually independent.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
P. Vopalensky and Z. Kozmik
Eye evolution: common use and independent recruitment of genetic components
Phil Trans R Soc B,
October 12, 2009;
364(1531):
2819 - 2832.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. D. Coletta, K. L. Christensen, D. S. Micalizzi, P. Jedlicka, M. Varella-Garcia, and H. L. Ford
Six1 Overexpression in Mammary Cells Induces Genomic Instability and Is Sufficient for Malignant Transformation
Cancer Res.,
April 1, 2008;
68(7):
2204 - 2213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-Q. Gong, A. R. Yallowitz, H. Sun, G. R. Dressler, and D. M. Wellik
A Hox-Eya-Pax Complex Regulates Early Kidney Developmental Gene Expression
Mol. Cell. Biol.,
November 1, 2007;
27(21):
7661 - 7668.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Barembaum and M. Bronner-Fraser
Spalt4 mediates invagination and otic placode gene expression in cranial ectoderm
Development,
November 1, 2007;
134(21):
3805 - 3814.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Schlosser
How old genes make a new head: redeployment of Six and Eya genes during the evolution of vertebrate cranial placodes
Integr. Comp. Biol.,
September 1, 2007;
47(3):
343 - 359.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Giordani, L. Bajard, J. Demignon, P. Daubas, M. Buckingham, and P. Maire
Six proteins regulate the activation of Myf5 expression in embryonic mouse limbs
PNAS,
July 3, 2007;
104(27):
11310 - 11315.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zhu, A. S. Gleiberman, and M. G. Rosenfeld
Molecular Physiology of Pituitary Development: Signaling and Transcriptional Networks
Physiol Rev,
July 1, 2007;
87(3):
933 - 963.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Behbakht, L. Qamar, C. S. Aldridge, R. D. Coletta, S. A. Davidson, A. Thorburn, and H. L. Ford
Six1 Overexpression in Ovarian Carcinoma Causes Resistance to TRAIL-Mediated Apoptosis and Is Associated with Poor Survival
Cancer Res.,
April 1, 2007;
67(7):
3036 - 3042.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Nechiporuk, T. Linbo, K. D. Poss, and D. W. Raible
Specification of epibranchial placodes in zebrafish
Development,
February 1, 2007;
134(3):
611 - 623.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Bricaud and A. Collazo
The Transcription Factor six1 Inhibits Neuronal and Promotes Hair Cell Fate in the Developing Zebrafish (Danio rerio) Inner Ear
J. Neurosci.,
October 11, 2006;
26(41):
10438 - 10451.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yu, E. Davicioni, T. J. Triche, and G. Merlino
The Homeoprotein Six1 Transcriptionally Activates Multiple Protumorigenic Genes but Requires Ezrin to Promote Metastasis
Cancer Res.,
February 15, 2006;
66(4):
1982 - 1989.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Riccomagno, S. Takada, and D. J. Epstein
Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh
Genes & Dev.,
July 1, 2005;
19(13):
1612 - 1623.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Bok, M. Bronner-Fraser, and D. K. Wu
Role of the hindbrain in dorsoventral but not anteroposterior axial specification of the inner ear
Development,
May 1, 2005;
132(9):
2115 - 2124.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Grifone, J. Demignon, C. Houbron, E. Souil, C. Niro, M. J. Seller, G. Hamard, and P. Maire
Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression during myogenesis in the mouse embryo
Development,
May 1, 2005;
132(9):
2235 - 2249.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Reichenberger, R. D. Coletta, A. P. Schulte, M. Varella-Garcia, and H. L. Ford
Gene Amplification Is a Mechanism of Six1 Overexpression in Breast Cancer
Cancer Res.,
April 1, 2005;
65(7):
2668 - 2675.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Kutejova, B. Engist, M. Mallo, B. Kanzler, and N. Bobola
Hoxa2 downregulates Six2 in the neural crest-derived mesenchyme
Development,
February 1, 2005;
132(3):
469 - 478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Silver and I. Rebay
Signaling circuitries in development: insights from the retinal determination gene network
Development,
January 1, 2005;
132(1):
3 - 13.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. F. Barald and M. W. Kelley
From placode to polarization: new tunes in inner ear development
Development,
September 1, 2004;
131(17):
4119 - 4130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. D. Coletta, K. Christensen, K. J. Reichenberger, J. Lamb, D. Micomonaco, L. Huang, D. M. Wolf, C. Muller-Tidow, T. R. Golub, K. Kawakami, et al.
The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin A1
PNAS,
April 27, 2004;
101(17):
6478 - 6483.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2003
