The fully linked HTML version of this article has now been published.
Development ePress online publication date 18 Feb 2004
doi: 10.1242/dev.01010
Research article
Discrete gene sets depend on POU domain transcription factor Brn3b/Brn-3.2/POU4f2 for their expression in the mouse embryonic retina
Xiuqian Mu,
Phillip D. Beremand,
Sheng Zhao,
Rashmi Pershad,
Hongxia Sun,
Ann Scarpa,
Shuguang Liang,
Terry L. Thomas,
and
William H. Klein*
* Author for correspondence (e-mail: wklein{at}mdanderson.org)
Brn3b/Brn-3.2/POU4f2 is a POU domain transcription factor that is essential for retinal ganglion cell (RGC) differentiation, axonal outgrowth and survival. Our goal was to establish a link between Brn3b and the downstream events leading to RGC differentiation. We sought to determine both the number and types of genes that depend on Brn3b for their expression. RNA probes from wild-type and Brn3b-/- E14.5, E16.5 and E18.5 mouse retinas were hybridized to a microarray containing 18,816 retina-expressed cDNAs. At E14.5, we identified 87 genes whose expression was significantly altered in the absence of Brn3b and verified the results by real-time PCR and in situ hybridization. These genes fell into discrete sets that encoded transcription factors, proteins associated with neuron integrity and function, and secreted signaling molecules. We found that Brn3b influenced gene expression in non RGCs of the retina by controlling the expression of secreted signaling molecules such as sonic hedgehog and myostatin/Gdf8. At later developmental stages, additional alterations in gene expression were secondary consequences of aberrant RGC differentiation caused by the absence of Brn3b. Our results demonstrate that a small but crucial fraction of the RGC transcriptome is dependent on Brn3b. The Brn3b-dependent gene sets therefore provide a unique molecular signature for the developing retina.
This article has been cited by other articles:
|
|
|
|
 
L. Pan, M. Deng, X. Xie, and L. Gan
ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells
Development,
June 1, 2008;
135(11):
1981 - 1990.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Mu, X. Fu, P. D. Beremand, T. L. Thomas, and W. H. Klein
Gene-regulation logic in retinal ganglion cell development: Isl1 defines a critical branch distinct from but overlapping with Pou4f2
PNAS,
May 13, 2008;
105(19):
6942 - 6947.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Qiu, H. Jiang, and M. Xiang
A Comprehensive Negative Regulatory Program Controlled by Brn3b to Ensure Ganglion Cell Specification from Multipotential Retinal Precursors
J. Neurosci.,
March 26, 2008;
28(13):
3392 - 3403.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-A. Mao, T. Kiyama, P. Pan, Y. Furuta, A.-K. Hadjantonakis, and W. H. Klein
Eomesodermin, a target gene of Pou4f2, is required for retinal ganglion cell and optic nerve development in the mouse
Development,
January 15, 2008;
135(2):
271 - 280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Soto, E. Oglesby, B. P. Buckingham, J. L. Son, E. D. O. Roberson, M. R. Steele, D. M. Inman, M. L. Vetter, P. J. Horner, and N. Marsh-Armstrong
Retinal Ganglion Cells Downregulate Gene Expression and Lose Their Axons within the Optic Nerve Head in a Mouse Glaucoma Model
J. Neurosci.,
January 9, 2008;
28(2):
548 - 561.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. V. Das, J. James, S. Bhattacharya, A. N. Imbalzano, M. L. Antony, G. Hegde, X. Zhao, K. Mallya, F. Ahmad, E. Knudsen, et al.
SWI/SNF Chromatin Remodeling ATPase Brm Regulates the Differentiation of Early Retinal Stem Cells/Progenitors by Influencing Brn3b Expression and Notch Signaling
J. Biol. Chem.,
November 30, 2007;
282(48):
35187 - 35201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Butler and G. Tear
Getting axons onto the right path: the role of transcription factors in axon guidance
Development,
February 1, 2007;
134(3):
439 - 448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Wang, G. D. Dakubo, S. Thurig, C. J. Mazerolle, and V. A. Wallace
Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina
Development,
November 15, 2005;
132(22):
5103 - 5113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. T. Nguyen, K. Cho, S. A. Stratton, and M. C. Barton
Transcription Factor Interactions and Chromatin Modifications Associated with p53-Mediated, Developmental Repression of the Alpha-Fetoprotein Gene
Mol. Cell. Biol.,
March 15, 2005;
25(6):
2147 - 2157.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. B. Bowman, S.-Y. Yoo, N. P. Dantuma, and H. Y. Zoghbi
Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation
Hum. Mol. Genet.,
March 1, 2005;
14(5):
679 - 691.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Pan, Z. Yang, L. Feng, and L. Gan
Functional equivalence of Brn3 POU-domain transcription factors in mouse retinal neurogenesis
Development,
February 15, 2005;
132(4):
703 - 712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. de Melo, G. Du, M. Fonseca, L.-A. Gillespie, W. J. Turk, J. L. R. Rubenstein, and D. D. Eisenstat
Dlx1 and Dlx2 function is necessary for terminal differentiation and survival of late-born retinal ganglion cells in the developing mouse retina
Development,
January 15, 2005;
132(2):
311 - 322.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Yu, S. He, J. S. Friedman, M. Akimoto, D. Ghosh, A. J. Mears, D. Hicks, and A. Swaroop
Altered Expression of Genes of the Bmp/Smad and Wnt/Calcium Signaling Pathways in the Cone-only Nrl-/- Mouse Retina, Revealed by Gene Profiling Using Custom cDNA Microarrays
J. Biol. Chem.,
October 1, 2004;
279(40):
42211 - 42220.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Eng, J. Lanier, N. Fedtsova, and E. E. Turner
Coordinated regulation of gene expression by Brn3a in developing sensory ganglia
Development,
August 15, 2004;
131(16):
3859 - 3870.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yoshida, A. J. Mears, J. S. Friedman, T. Carter, S. He, E. Oh, Y. Jing, R. Farjo, G. Fleury, C. Barlow, et al.
Expression profiling of the developing and mature Nrl-/- mouse retina: identification of retinal disease candidates and transcriptional regulatory targets of Nrl
Hum. Mol. Genet.,
July 15, 2004;
13(14):
1487 - 1503.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2004
