Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens

Cvekl, Aleš; Yang, Ying; Chauhan, Bharesh K.; Cveklova, Kveta

doi:10.1387/ijdb.041866ac

Cited by 90 publications

(81 citation statements)

References 172 publications

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“…In striking contrast to the conservation of opsins as the visual pigments in the PRCs, the lens crystallins are diverse proteins that are often taxon-specific, i.e., entirely different proteins function as crystallins in different species. Similar transcription factors including those of the Pax gene family have been independently recruited for the regulation of nonhomologous crystallin genes in Tripedalia and vertebrates (30,42,43) to achieve a gradient of refractive index within their transparent lenses. The independent recruitment of lens crystallins is consistent with parallel evolution of cubozoan and vertebrate eyes and provides a striking example of the role of convergence in eye evolution.…”

Section: Discussionmentioning

confidence: 99%

Assembly of the cnidarian camera-type eye from vertebrate-like components

Kozmík

Růžičková

Jonasova

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

117

113

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Animal eyes are morphologically diverse. Their assembly, however, always relies on the same basic principle, i.e., photoreceptors located in the vicinity of dark shielding pigment. Cnidaria as the likely sister group to the Bilateria are the earliest branching phylum with a well developed visual system. Here, we show that cameratype eyes of the cubozoan jellyfish, Tripedalia cystophora, use genetic building blocks typical of vertebrate eyes, namely, a ciliary phototransduction cascade and melanogenic pathway. Our findings indicative of parallelism provide an insight into eye evolution. Combined, the available data favor the possibility that vertebrate and cubozoan eyes arose by independent recruitment of orthologous genes during evolution.T he assembly of diverse animal eyes requires two fundamental building blocks, photoreceptors and dark shielding pigment. The function of photoreceptors is to convert light (stream of photons) into intracellular signaling. The photoreceptor cells (PRCs) are classified into two distinct types: rhabdomeric, characteristic of vision in invertebrate eyes; and ciliary, characteristic of vision in vertebrate eyes (1). In both ciliary and rhabdomeric PRCs, the seven-transmembrane receptor (opsin) associates with retinal to constitute a functional photosensitive pigment. Each photoreceptor type uses a separate phototransduction cascade. Rhabdomeric photoreceptors employ r-opsins and a phospholipase C cascade, whereas ciliary photoreceptors use c-opsins and a phosphodiesterase (PDE) cascade (2, 3). In general, the dark pigment reduces photon scatter and orients the direction optimally sensitive to light. The biochemical nature of the dark pigment appears more diverse than the phototransduction cascades used by the PRCs. Vertebrate eyes use melanin as their exclusive dark pigment. However, among invertebrates, pterins constitute the eye pigment in the polychaete Platynereis dumerilii (4), pterins and ommochromes are accumulated in eyes of Drosophila (5), and melanin is found rarely such as in the inverse cup-like eyes of the planarian, Dugesia (6).Cnidaria, the likely sister group to the Bilateria, constitute the earliest branching phylum containing a well developed visual system. For example, Cubozoa (known as ''box jellyfish'') have camera-type eyes with cornea, lens, and retina; unexpectedly, the cubozoan retina has ciliated PRCs that are typical for vertebrate eyes (7-9). Cubomedusae are active swimmers that are able to make directional changes in response to visual stimuli (10). The cubozoan jellyfish, Tripedalia cystophora (Fig. 1A), has four sensory structures called rhopalia that are equally spaced around the bell. In addition to two camera-type lens containing eyes at right angles to one another, each rhopalium has two pit-shaped and two slit-shaped pigment cup eyes (Fig. 1B). Thus, with six eyes located on each rhopalium, Tripedalia has 24 eyes altogether. Because the visual fields of individual eyes of the rhopalium partly overlap, Tripedalia (like other Cubomedusae) has an al...

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Section: Discussionmentioning

confidence: 99%

Assembly of the cnidarian camera-type eye from vertebrate-like components

Kozmík

Růžičková

Jonasova

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

117

113

View full text Add to dashboard Cite

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“…The expression patterns of individual mammalian β/γ-crystallin (βA3/A1, βA2, βA4, βB1, βB2, βB3, γA, γB, γC, γD, γE, γF and γS) genes have not been determined with the full precision. In general, β/γ-crystallin genes are highly expressed in lens fiber cells with no detectable or low expression in lens epithelium (see Cvekl et al, 2004). Expression of rat and mouse βB1-crystallin, probed by in situ hybridization, was found in fully elongated primary lens fiber cells and no expression was found in the embryonic lens epithelium while βB2-crystallin expression does not initiate until after birth in rodents (Ueda et al, 2002).…”

Section: Temporal and Spatial Expression Of Crystallins In Mouse And mentioning

confidence: 99%

Genetic and epigenetic mechanisms of gene regulation during lens development

Cvekl

Duncan

2007

Progress in Retinal and Eye Research

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139

124

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Recent studies demonstrated a number of links between chromatin structure, gene expression, extracellular signaling and cellular differentiation during lens development. Lens progenitor cells originate from a pool of common progenitor cells, the pre-placodal region (PPR) which is formed due to a complex exchange of extracellular signals between the neural plate, naïve ectoderm and mesendoderm. A specific commitment to the lens program over alternate choices such as the formation of olfactory epithelium or the anterior pituitary is manifested by the formation of a thickened surface ectoderm, the lens placode. Mouse lens progenitor cells are characterized by the expression of a complement of lens lineage-specific transcription factors including Pax6, Six3 and Sox2, controlled by FGF and BMP signaling, followed later by c-Maf, Mab21like1, Prox1 and FoxE3. Proliferation of lens progenitors together with their morphogenetic movements results in the formation of the lens vesicle. This transient structure, comprised of lens precursor cells, is polarized with its anterior cells retaining their epithelial morphology and proliferative capacity, whereas the posterior lens precursor cells initiate terminal differentiation forming the primary lens fibers. Lens differentiation is marked by expression and accumulation of crystallins and other structural proteins. The transcriptional control of crystallin genes is characterized by the reiterative use of transcription factors required for the establishment of lens precursors in combination with more ubiquitously expressed factors (e.g. AP-1, AP-2α, CREB and USF) and recruitment of histone acetyltransferases (HATs) CBP and p300, and chromatin remodeling complexes SWI/SNF and ISWI. These studies have poised the study of lens development at the forefront of efforts to understand the connections between development, cell signaling, gene transcription and chromatin remodeling.

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“…6 A promoter fragment of −88 to +46 is sufficient to support lens-specific expression of the chloramphenicol acetyl transferase (CAT) reporter gene. 17 Transcription factors regulating in vivo expression of this gene emerged from gene targeting studies of lens lineage-specifying genes described above.…”

Section: Introductionmentioning

confidence: 99%

Tissue-specific Regulation of the Mouse αA-crystallin Gene in Lens via Recruitment of Pax6 and c-Maf to its Promoter

Yang

Cvekl

2005

Journal of Molecular Biology

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Pax6 is a lineage-restricted DNA-binding transcription factor regulating the formation of mammalian organs including brain, eye and pancreas. Pax6 plays key roles during the initial formation of lens lineage, proliferation of lens progenitor and precursor cells and their terminal differentiation. In addition to Pax6, lens fiber cell differentiation is regulated by c-Maf, Prox1 and Sox1. Crystallins are essential lens structural proteins required for light refraction and transparency. Mouse αA-crystallin represents about 17% of all crystallins at the protein level and ranks as one of the most abundant tissue-specific proteins. Lens-specific expression of this gene is regulated at the level of transcription. A promoter fragment of −88 to +46 is capable of driving lens-specific expression in transgenic mouse. Here we provide data suggesting that this lens-specific promoter fragment is comprised of multiple Pax6 and Maf-binding sites. Site-directed mutagenesis of regions within these sites resulted in partially or completely reduced promoter activities in lens cells. Co-transfections using Pax6 and c-Maf alone revealed moderate and strong activations of this promoter, respectively. In contrast to synergistic activation of αB-crystallin by Pax6 and c-Maf, Pax6 has a neutral effect on c-Maf-mediated αA-crystallin promoter activation. Chromatin immunoprecipitations established in vivo interactions of Pax6 and c-Maf with the αA-crystallin promoter in lens cells. Collectively, the present data support a molecular model in which tissue-specific expression of αA-crystallin is regulated by recruitment of Pax6 and c-Maf, two proteins regulating multiple processes of lens differentiation, to its promoter. In addition, the data suggest a molecular model of temporal and spatial regulation of αB, αA and γ-crystallin genes in mouse embryonic lens by using variants of the Pax6/ Maf regulatory module.

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Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens

Cited by 90 publications

References 172 publications

Assembly of the cnidarian camera-type eye from vertebrate-like components

Assembly of the cnidarian camera-type eye from vertebrate-like components

Genetic and epigenetic mechanisms of gene regulation during lens development

Tissue-specific Regulation of the Mouse αA-crystallin Gene in Lens via Recruitment of Pax6 and c-Maf to its Promoter

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