|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
1 Division of Developmental Biology and Department of Ophthalmology, Children’s Hospital Research Foundation, 3333 Burnet Avenue Cincinnati, OH 45229, USA
2 Division of Human and Molecular Genetics, Children’s Research Institute, 700 Children’s Drive, Columbus, OH 43205, USA
3 The Neurosciences Institute, 10640 John Jay Hopkins Drive, San Diego, CA 92121, USA
*Author for correspondence (e-mail: richard.lang{at}chmcc.org)
Accepted 30 April 2002
We have investigated the role of Bmp signaling in development of the mouse lens using three experimental strategies. First, we have shown that the Bmp ligand inhibitor noggin can suppress the differentiation of primary lens fiber cells in explant culture. Second, we have expressed a dominant-negative form of the type 1 Bmp family receptor Alk6 (Bmpr1b – Mouse Genome Informatics) in the lens in transgenic mice and shown that an inhibition of primary fiber cell differentiation can be detected at E13.5. Interestingly, the observed inhibition of primary fiber cell development was asymmetrical and appeared only on the nasal side of the lens in the ventral half. Expression of the inhibitory form of Alk6 was driven either by the 
A-cystallin promoter or the ectoderm enhancer from the Pax6 gene in two different transgenes. These expression units drive transgene expression in distinct patterns that overlap in the equatorial cells of the lens vesicle at E12.5. Despite the distinctions between the transgenes, they caused primary fiber cell differentiation defects that were essentially identical, which implied that the equatorial lens vesicle cells were responding to Bmp signals in permitting primary fiber cells to develop. Importantly, E12.5 equatorial lens vesicle cells showed cell-surface immunoreactivity for bone-morphogenetic protein receptor type 2 and nuclear immunoreactivity for the active, phosphorylated form of the Bmp responsive Smads. This indicated that these cells had the machinery for Bmp signaling and were responding to Bmp signals. We conclude that Bmp signaling is required for primary lens fiber cell differentiation and, given the asymmetry of the differentiation inhibition, that distinct differentiation stimuli may be active in different quadrants of the eye.
Key words: Bmp, Mouse, Lens, Alk6
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Rajagopal, L. K. Dattilo, V. Kaartinen, C.-X. Deng, L. Umans, A. Zwijsen, A. B. Roberts, E. P. Bottinger, and D. C. Beebe Functions of the Type 1 BMP Receptor Acvr1 (Alk2) in Lens Development: Cell Proliferation, Terminal Differentiation, and Survival Invest. Ophthalmol. Vis. Sci., November 1, 2008; 49(11): 4953 - 4960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Boswell, P. J. Lein, and L. S. Musil Cross-Talk between Fibroblast Growth Factor and Bone Morphogenetic Proteins Regulates Gap Junction-mediated Intercellular Communication in Lens Cells Mol. Biol. Cell, June 1, 2008; 19(6): 2631 - 2641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Wordinger and A. F. Clark Bone Morphogenetic Proteins and Their Receptors in the Eye Experimental Biology and Medicine, September 1, 2007; 232(8): 979 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Pan, A. Woodbury, J. D. Esko, K. Grobe, and X. Zhang Heparan sulfate biosynthetic gene Ndst1 is required for FGF signaling in early lens development Development, December 15, 2006; 133(24): 4933 - 4944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yoshimoto, Y. Saigou, Y. Higashi, and H. Kondoh Regulation of ocular lens development by Smad-interacting protein 1 involving Foxe3 activation Development, October 15, 2005; 132(20): 4437 - 4448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dutta, J.-E. Dietrich, G. Aspock, R. D. Burdine, A. Schier, M. Westerfield, and Z. M. Varga pitx3 defines an equivalence domain for lens and anterior pituitary placode Development, April 1, 2005; 132(7): 1579 - 1590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Gotoh, M. Ito, S. Yamamoto, I. Yoshino, N. Song, Y. Wang, I. Lax, J. Schlessinger, M. Shibuya, and R. A. Lang Tyrosine phosphorylation sites on FRS2{alpha} responsible for Shp2 recruitment are critical for induction of lens and retina PNAS, December 7, 2004; 101(49): 17144 - 17149. [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]
|
|
|
|
|
|
N. Golestaneh, J. Fan, R. N. Fariss, W.-K. Lo, P. S. Zelenka, and A. B. Chepelinsky Lens Major Intrinsic Protein (MIP)/Aquaporin 0 Expression in Rat Lens Epithelia Explants Requires Fibroblast Growth Factor-induced ERK and JNK Signaling J. Biol. Chem., July 23, 2004; 279(30): 31813 - 31822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Lovicu, P. Steven, S. Saika, and J. W. McAvoy Aberrant Lens Fiber Differentiation in Anterior Subcapsular Cataract Formation: A Process Dependent on Reduced Levels of Pax6 Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 1946 - 1953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lyu and C.-K. Joo Wnt signaling enhances FGF2-triggered lens fiber cell differentiation Development, April 15, 2004; 131(8): 1813 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Oka, R. Tsujimoto, M. Kajikawa, K. Koshiba-Takeuchi, J. Ina, M. Yano, A. Tsuchiya, Y. Ueta, A. Soma, H. Kanda, et al. HtrA1 serine protease inhibits signaling mediated by Tgf{beta} family proteins Development, March 1, 2004; 131(5): 1041 - 1053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Simon and T. Lufkin Postnatal Lethality in Mice Lacking the Sax2 Homeobox Gene Homologous to Drosophila S59/slouch: Evidence for Positive and Negative Autoregulation Mol. Cell. Biol., December 15, 2003; 23(24): 9046 - 9060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chandrasekher and D. Sailaja Differential Activation of Phosphatidylinositol 3-Kinase Signaling during Proliferation and Differentiation of Lens Epithelial Cells Invest. Ophthalmol. Vis. Sci., October 1, 2003; 44(10): 4400 - 4411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-Y. Wu, M. Li, D. R. Hinton, L. Guo, S. Jiang, J. T. Wang, A. Zeng, J. B. Xie, M. Snead, C. Shuler, et al. Microphthalmia Resulting from Msx2-Induced Apoptosis in the Optic Vesicle Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2404 - 2412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Weston, A. Wong, J. P. Hall, M. E.P. Goad, R. A. Flavell, and R. J. Davis JNK initiates a cytokine cascade that causes Pax2 expression and closure of the optic fissure Genes & Dev., May 15, 2003; 17(10): 1271 - 1280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-X. Huang, M. Feldmeier, Y.-B. Shui, and D. C. Beebe Evaluation of Fibroblast Growth Factor Signaling during Lens Fiber Cell Differentiation Invest. Ophthalmol. Vis. Sci., February 1, 2003; 44(2): 680 - 690. [Abstract] [Full Text] [PDF]
|
|
