Ectopic Pax6 Expression Disturbs Lens Fiber Cell Differentiation

Duncan, Melinda K.; Xie, Leike; David, Larry L.; Robinson, Michael L.; Taube, Jennifer R.; Cui, Wenwu; Reneker, Lixing W.

doi:10.1167/iovs.04-0151

Cited by 47 publications

(59 citation statements)

References 56 publications

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“…Mutation of these factors causes cataracts in both mouse models and humans (Glaser et al, 1994;Hanson et al, 1994;Semina et al, 1998;Wigle et al, 1999;Blixt et al, 2000;Brownell et al, 2000;Duncan et al 2000;Ring et al, 2000;Semina et al, 2000Semina et al, , 2001Jamieson et al, 2002;Lyon et al, 2003;Berry et al, 2004;Duncan et al, 2004;Rajaram and Kerpolla, 2004). Most of these transcription factors are downstream of Pax6 in the lens.…”

Section: Resultsmentioning

confidence: 99%

“…Pax6 is upstream of Sox2 (Furuta and Hogan, 1998), Pax6 and Sox2 cooperatively regulate gene expression (Kamachi et al 2001, Aota et al, 2003, and Sox2 is required for the maintenance of Pax6 (Donner et al, in press). Appropriate temporal, spatial, and quantitative control of Pax6 expression is required for appropriate lens morphogenesis (Hill et al, 1991;Glaser et al, 1994;Hanson et al, 1994;Grindley et al, 1995;Quinn et al, 1996;Schedl et al, 1996;Brown et al, 1998;Ashery-Padan et al, 2000;Duncan et al, 2000;van Raamsdonk and Tilgham, 2000;Dimanlig et al, 2001;Duncan et al, 2004). PAX6 mutation is causative for several congenital eye defects in humans including aniridia, Peters' anomaly and cataract (reviewed in Prosser and van Heyningen, 1998).…”

Section: Resultsmentioning

confidence: 99%

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Pax6 is misexpressed in Sox1 null lens fiber cells

Donner

Episkopou

et al. 2007

Gene Expression Patterns

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Sox1 null lens fiber cells fail to elongate and have disrupted expression of gamma crystallin. We have evaluated the expression of Sox1 and Pax6 proteins during critical stages of lens morphogenesis, with particular focus on fiber cell differentiation. While Pax6 and Sox1 are co-expressed during early stages of fiber cell differentiation, Sox1 up-regulation coincides temporally with the down-regulation of Pax6, and these proteins therefore display a striking inverse expression pattern in the lens fiber cell compartment. Furthermore, Pax6 is inappropriately expressed in the fiber cells of Sox1 null mice and the Pax6 target, α5 integrin, is simultaneously misexpressed. Finally, we demonstrate a genetic interaction between Sox1 and Pax6, as Sox1 heterozygosity partially rescues the diameter of Pax6 Sey lenses by increasing the number of cells in the fiber cell compartment.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Pax6 is misexpressed in Sox1 null lens fiber cells

Donner

Episkopou

et al. 2007

Gene Expression Patterns

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“…GAD65, EGAD, and GABA were initially detected in the lens placode, which is the site of expression of multiple transcription factors known as regulators of lens induction and fiber cell differentiation, such as Pax6, Six3, Eya, Dach1, Mafs, Sox2, Sox3, and Prox1 (Kawauchi et al, 1999;Kim et al, 1999;Wigle et al, 1999;Ogino and Yasuda, 2000;Ring et al, 2000;Duncan et al, 2002Duncan et al, , 2004Cui et al, 2004;Purcell et al, 2005). Pax6, Sox, c-Maf, and Prox1 have consensus binding sites in conserved regions of GAD65 and GAD67 genes (F. Erdélyi and Z.D.…”

Section: Transcriptional Regulation Of Gad In the Lens: Involvement Omentioning

confidence: 99%

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

Kwakowsky

Schwirtlich

Zhang

et al. 2007

Developmental Dynamics

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Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter of the adult nervous system and its biosynthetic enzyme glutamic acid decarboxylase (GAD) are abundantly expressed in the embryonic nervous system and are involved in the modulation of cell proliferation, migration, and differentiation. Here we describe for the first time the expression of GABA and embryonic and adult GAD isoforms in the developing mouse lens. We show that the GAD isoforms are sequentially induced with specific spatiotemporal profiles: GAD65 and embryonic GAD isoforms prevail in primary fibers, while GAD67 is the predominant GAD expressed in the postnatal secondary fibers. This pattern correlates well with the expression of Dlx2 and Dlx5, known as upstream regulators of GAD. GABA and GAD are most abundant at the tips of elongating fibers and are absent from organelle-free cells, suggesting their involvement is primarily in shaping of the cytoskeleton during fiber elongation stages. Developmental Dynamics 236: 3532-3544, 2007.

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“…Normal development of the inner retina is directly influenced by a well-elaborated spatial and temporal pattern of PAX6 expression. 1,[6][7][8][9][19][20][21] However, little is known about PAX6 expression and function in the adult mammalian retina. De Melo et al 22 showed that several homeobox genes including Pax6 are expressed in the young adult mouse retina and we recently reported continuous expression of PAX6 in the young, adult, and old normal human retina.…”

Section: Pax6 Expression and Retinal Cell Death In A Transgenicmentioning

confidence: 99%

PAX6 Expression and Retinal Cell Death in a Transgenic Mouse Model for Acute Angle-Closure Glaucoma

Stanescu-Segall¹,

Birke²,

Wenzel

et al. 2015

Journal of Glaucoma

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PURPOSE: PAX6 is a highly conserved protein essential for the control of eye development both in invertebrates and vertebrates. PAX6 expression persists in the adult inner retina, but little is known about its functions after completion of retinal differentiation. Therefore, we investigated PAX6 expression in wild-type and calcitonin receptor-like receptor transgenic (CLR) mice with angle-closure glaucoma. METHODS: Intraocular pressure was measured by indentation tonometry in anesthetized mice. Eyes of mice of both genotypes were enucleated at various ages and retinas were processed for morphological analysis and PAX6 immunostaining. The content of PAX6 in retinal extracts was estimated by Western blot analysis. Retinal expression of glaucoma-related genes was analyzed by reverse transcription-polymerase chain reaction. RESULTS: Control mice showed normal retinal morphology between p22 and p428 with steady PAX6 expression in the ganglion cell layer (GCL) and the inner nuclear layer (INL). CLR mice examined between p22 and p82 exhibited increased intraocular pressure and a progressive decrease in cell number including PAX6-expressing cells in the GCL. Originally published at: Stanescu-Segall, Dinu; Birke, Kerstin; Wenzel, Andreas; Grimm, Christian; Orgul, Sorguel; Fischer, Jan A; Born, Walter; Hafezi, Farhad (2015). PAX6 expression and retinal cell death in a transgenic mouse model for acute angle-closure glaucoma. Journal of Glaucoma, 24(6):426-432.

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Ectopic Pax6 Expression Disturbs Lens Fiber Cell Differentiation

Abstract: The data demonstrate that high levels of Pax6 expression disrupt normal fiber cell differentiation and maturation.

Cited by 47 publications

References 56 publications

Pax6 is misexpressed in Sox1 null lens fiber cells

Pax6 is misexpressed in Sox1 null lens fiber cells

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

PAX6 Expression and Retinal Cell Death in a Transgenic Mouse Model for Acute Angle-Closure Glaucoma

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