The fully linked HTML version of this article has now been published.
Development ePress online publication date 29 Jun 2005
doi: 10.1242/dev.01917
Research article
Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation
Nan Gao,
Kenichiro Ishii,
Janni Mirosevich,
Satoru Kuwajima,
Stacey R. Oppenheimer,
Richard L. Roberts,
Ming Jiang,
Xiuping Yu,
Scott B. Shappell,
Richard M. Caprioli,
Markus Stoffel,
Simon W. Hayward,
and
Robert J. Matusik*
* Author for correspondence (e-mail: robert.matusik{at}vanderbilt.edu)
We have previously shown that a forkhead transcription factor Foxa1 interacts with androgen signaling and controls prostate differentiated response. Here, we show the mouse Foxa1 expression marks the entire embryonic urogenital sinus epithelium (UGE), contrasting with Shh and Foxa2, which are restricted to the basally located cells during prostate budding. The Foxa1-deficient mouse prostate shows a severely altered ductal pattern that resembles primitive epithelial cords surrounded by thick stromal layers. Characterization of these mutant cells indicates a population of basal-like cells similar to those found in the embryonic UGE, whereas no differentiated or mature luminal epithelial cells are found in Foxa1-deficient epithelium. These phenotypic changes are accompanied with molecular aberrations, including focal epithelial activation of Shh and elevated Foxa2 and Notch1 in the null epithelium. Perturbed epithelial-stromal interactions induced by Foxa1-deficient epithelium is evident, as demonstrated by the expansion of surrounding smooth muscle and elevated levels of stromal factors (Bmp4, Fgf7, Fgf10 and Gli). The prostatic homeobox protein Nkx3.1, a known proliferation inhibitor, was downregulated in Foxa1-deficient epithelial cells, while several prostate-specific androgen-regulated markers, including a novel Foxa1 target, are absent in the null prostate. These data indicate that Foxa1 plays a pivotal role in controlling prostate morphogenesis and cell differentiation.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
Q. Sun, X. Yu, D. J. Degraff, and R. J. Matusik
Upstream Stimulatory Factor 2, a Novel FoxA1-Interacting Protein, Is Involved in Prostate-Specific Gene Expression
Mol. Endocrinol.,
December 1, 2009;
23(12):
2038 - 2047.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kunisada, C.-Y. Cui, Y. Piao, M. S.H. Ko, and D. Schlessinger
Requirement for Shh and Fox family genes at different stages in sweat gland development
Hum. Mol. Genet.,
May 15, 2009;
18(10):
1769 - 1778.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Gao, J. LeLay, M. Z. Vatamaniuk, S. Rieck, J. R. Friedman, and K. H. Kaestner
Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development
Genes & Dev.,
December 15, 2008;
22(24):
3435 - 3448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Jin, Y. Lho, L. Connelly, Y. Wang, X. Yu, L. Saint Jean, T. C. Case, K. Ellwood-Yen, C. L. Sawyers, N. A. Bhowmick, et al.
The Nuclear Factor-{kappa}B Pathway Controls the Progression of Prostate Cancer to Androgen-Independent Growth
Cancer Res.,
August 15, 2008;
68(16):
6762 - 6769.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L.-j. Shao, H. Y. Shi, G. Ayala, D. Rowley, and M. Zhang
Haploinsufficiency of the Maspin Tumor Suppressor Gene Leads to Hyperplastic Lesions in Prostate
Cancer Res.,
July 1, 2008;
68(13):
5143 - 5151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Jin, Y. Lho, Y. Wang, M. Ao, M. P. Revelo, S. W. Hayward, M. L. Wills, S. K. Logan, P. Zhang, and R. J. Matusik
Down-regulation of p57Kip2 Induces Prostate Cancer in the Mouse
Cancer Res.,
May 15, 2008;
68(10):
3601 - 3608.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M A Thorat, C Marchio, A Morimiya, K Savage, H Nakshatri, J S Reis-Filho, and S Badve
Forkhead box A1 expression in breast cancer is associated with luminal subtype and good prognosis
J. Clin. Pathol.,
March 1, 2008;
61(3):
327 - 332.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Badve, D. Turbin, M. A. Thorat, A. Morimiya, T. O. Nielsen, C. M. Perou, S. Dunn, D. G. Huntsman, and H. Nakshatri
FOXA1 Expression in Breast Cancer Correlation with Luminal Subtype A and Survival
Clin. Cancer Res.,
August 1, 2007;
13(15):
4415 - 4421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Yu, K. Suzuki, Y. Wang, A. Gupta, R. Jin, M.-C. Orgebin-Crist, and R. Matusik
The Role of Forkhead Box A2 to Restrict Androgen-Regulated Gene Expression of Lipocalin 5 in the Mouse Epididymis
Mol. Endocrinol.,
October 1, 2006;
20(10):
2418 - 2431.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. O. Gillard and A. G. Farr
Features of Medullary Thymic Epithelium Implicate Postnatal Development in Maintaining Epithelial Heterogeneity and Tissue-Restricted Antigen Expression
J. Immunol.,
May 15, 2006;
176(10):
5815 - 5824.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2005
