QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

doi: 10.1242/10.1242/dev.00275

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Green, E. S. Articles by Levine, E. M. Search for Related Content PubMed PubMed Citation Articles by Green, E. S. Articles by Levine, E. M. Social Bookmarking                         What's this?

Genetic rescue of cell number in a mouse model of microphthalmia: interactions between Chx10 and G1-phase cell cycle regulators

¹ Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, UT 84132, USA
² Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132, USA

^* Author for correspondence (e-mail: elevine{at}hmbg.utah.edu)

Accepted 31 October 2002

Insufficient cell number is a primary cause of failed retinal development in the Chx10 mutant mouse. To determine if Chx10 regulates cell number by antagonizing p27^Kip1 activity, we generated Chx10, p27^Kip1 double null mice. The severe hypocellular defect in Chx10 single null mice is alleviated in the double null, and while Chx10-null retinas lack lamination, double null retinas have near normal lamination. Bipolar cells are absent in the double null retina, a defect that is attributable to a requirement for Chx10 that is independent of p27^Kip1. We find that p27^Kip1 is abnormally present in progenitors of Chx10-null retinas, and that its ectopic localization is responsible for a significant amount of the proliferation defect in this microphthalmia model system. mRNA and protein expression patterns in these mice and in cyclin D1-null mice suggest that Chx10 influences p27^Kip1 at a post-transcriptional level, through a mechanism that is largely dependent on cyclin D1. This is the first report of rescue of retinal proliferation in a microphthalmia model by deletion of a cell cycle regulatory gene.

Key words: Proliferation, Cell cycle, Cyclin-dependent kinase inhibitor, Ocular retardation, Microphthalmia, Homeobox, Retina, Chx10, p27^Kip1, Cyclin D1

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				D. S. Kim, T. Matsuda, and C. L. Cepko A Core Paired-Type and POU Homeodomain-Containing Transcription Factor Program Drives Retinal Bipolar Cell Gene Expression J. Neurosci., July 30, 2008; 28(31): 7748 - 7764. [Abstract] [Full Text] [PDF]

				K. Bharti, W. Liu, T. Csermely, S. Bertuzzi, and H. Arnheiter Alternative promoter use in eye development: the complex role and regulation of the transcription factor MITF Development, March 15, 2008; 135(6): 1169 - 1178. [Abstract] [Full Text] [PDF]

				P. Heine, E. Dohle, K. Bumsted-O'Brien, D. Engelkamp, and D. Schulte Evidence for an evolutionary conserved role of homothorax/Meis1/2 during vertebrate retina development Development, March 1, 2008; 135(5): 805 - 811. [Abstract] [Full Text] [PDF]

				R. A.P. Martins, F. Zindy, S. Donovan, J. Zhang, S. Pounds, A. Wey, P. S. Knoepfler, R. N. Eisenman, M. F. Roussel, and M. A. Dyer N-myc coordinates retinal growth with eye size during mouse development Genes & Dev., January 15, 2008; 22(2): 179 - 193. [Abstract] [Full Text] [PDF]

				I. Livne-bar, M. Pacal, M. C. Cheung, M. Hankin, J. Trogadis, D. Chen, K. M. Dorval, and R. Bremner Chx10 is required to block photoreceptor differentiation but is dispensable for progenitor proliferation in the postnatal retina PNAS, March 28, 2006; 103(13): 4988 - 4993. [Abstract] [Full Text] [PDF]

				N. S. Dhomen, K. S. Balaggan, R. A. Pearson, J. W. Bainbridge, E. M. Levine, R. R. Ali, and J. C. Sowden Absence of Chx10 Causes Neural Progenitors to Persist in the Adult Retina Invest. Ophthalmol. Vis. Sci., January 1, 2006; 47(1): 386 - 396. [Abstract] [Full Text] [PDF]

				S. K. Knauer, G. Carra, and R. H. Stauber Nuclear Export Is Evolutionarily Conserved in CVC Paired-Like Homeobox Proteins and Influences Protein Stability, Transcriptional Activation, and Extracellular Secretion Mol. Cell. Biol., April 1, 2005; 25(7): 2573 - 2582. [Abstract] [Full Text] [PDF]

				D. Murali, S. Yoshikawa, R. R. Corrigan, D. J. Plas, M. C. Crair, G. Oliver, K. M. Lyons, Y. Mishina, and Y. Furuta Distinct developmental programs require different levels of Bmp signaling during mouse retinal development Development, March 1, 2005; 132(5): 913 - 923. [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]

				D. J. Horsford, M.-T. T. Nguyen, G. C. Sellar, R. Kothary, H. Arnheiter, and R. R. McInnes Chx10 repression of Mitf is required for the maintenance of mammalian neuroretinal identity Development, January 1, 2005; 132(1): 177 - 187. [Abstract] [Full Text] [PDF]

				C Y Gregory-Evans, M J Williams, S Halford, and K Gregory-Evans Ocular coloboma: a reassessment in the age of molecular neuroscience J. Med. Genet., December 1, 2004; 41(12): 881 - 891. [Abstract] [Full Text] [PDF]

				S. Rowan, C.-M. A. Chen, T. L. Young, D. E. Fisher, and C. L. Cepko Transdifferentiation of the retina into pigmented cells in ocular retardation mice defines a new function of the homeodomain gene Chx10 Development, October 15, 2004; 131(20): 5139 - 5152. [Abstract] [Full Text] [PDF]

				T. Miyawaki, A. Uemura, M. Dezawa, R. T. Yu, C. Ide, S. Nishikawa, Y. Honda, Y. Tanabe, and T. Tanabe Tlx, an Orphan Nuclear Receptor, Regulates Cell Numbers and Astrocyte Development in the Developing Retina J. Neurosci., September 15, 2004; 24(37): 8124 - 8134. [Abstract] [Full Text] [PDF]

				Y. Tabata, Y. Ouchi, H. Kamiya, T. Manabe, K.-i. Arai, and S. Watanabe Specification of the Retinal Fate of Mouse Embryonic Stem Cells by Ectopic Expression of Rx/rax, a Homeobox Gene Mol. Cell. Biol., May 15, 2004; 24(10): 4513 - 4521. [Abstract] [Full Text] [PDF]

				E. M. Levine Cell cycling through development Development, May 15, 2004; 131(10): 2241 - 2246. [Abstract] [Full Text] [PDF]

				J. N. Kay, T. Roeser, J. S. Mumm, L. Godinho, A. Mrejeru, R. O. L. Wong, and H. Baier Transient requirement for ganglion cells during assembly of retinal synaptic layers Development, March 15, 2004; 131(6): 1331 - 1342. [Abstract] [Full Text] [PDF]

				R. L. Chow, B. Volgyi, R. K. Szilard, D. Ng, C. McKerlie, S. A. Bloomfield, D. G. Birch, and R. R. McInnes Control of late off-center cone bipolar cell differentiation and visual signaling by the homeobox gene Vsx1 PNAS, February 10, 2004; 101(6): 1754 - 1759. [Abstract] [Full Text] [PDF]

				A. D. Rutherford, N. Dhomen, H. K. Smith, and J. C. Sowden Delayed Expression of the Crx Gene and Photoreceptor Development in the Chx10-Deficient Retina Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 375 - 384. [Abstract] [Full Text] [PDF]

				S. M. Carcieri, A. L. Jacobs, and S. Nirenberg Classification of Retinal Ganglion Cells: A Statistical Approach J Neurophysiol, September 1, 2003; 90(3): 1704 - 1713. [Abstract] [Full Text] [PDF]