A highly conserved lens transcriptional control element from the Pax-6 gene

Williams, Sonya C.; Altmann, Curtis R.; Chow, Robert L.; Hemmati‐Brivanlou, Ali; Lang, Richard A.

doi:10.1016/s0925-4773(98)00057-4

Cited by 139 publications

(121 citation statements)

References 16 publications

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“…9). The ectodermal enhancer (EE) was shown to direct Pax6 expression in the surface ectoderm, lens and cornea (Kammandel et al, 1999;Williams et al, 1998). The EE contains binding sites for the Meis (Zhang et al, 2002), Sox (Aota et al, 2003;Donner et al, 2006a), Six3 and Oct family of proteins (Donner et al, 2006a), as well as a single Pax6-binding site (Aota et al, 2003).…”

Section: Regulation Of Pax6 Gene Expression In Lens-thementioning

confidence: 99%

Genetic and epigenetic mechanisms of gene regulation during lens development

Cvekl

Duncan

2007

Progress in Retinal and Eye Research

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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Section: Regulation Of Pax6 Gene Expression In Lens-thementioning

confidence: 99%

Genetic and epigenetic mechanisms of gene regulation during lens development

Cvekl

Duncan

2007

Progress in Retinal and Eye Research

139

124

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“…The identification of transcription control elements in Pax6 has rested on the simple strategy of sequence alignment to identify conserved regions and functional assessment using transgenic reporter constructs (Williams et al, 1998;Kammandel et al, 1999;Xu et al, 1999). If long-range sequence alignments are generated to compare the mouse and human Pax6 genes, it immediately becomes apparent that transcriptional regulation of this gene is complex.…”

Section: Pax6 Expression In the Lens Lineage Is Controlled By At Leasmentioning

confidence: 99%

Pathways regulating lens induction in the mouse

2004

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For more than a century, the lens has provided a relatively simple structure in which to study developmental mechanisms. Lens induction, where adjacent tissues signal the cell fate changes that result in lens formation, have been of particular interest. Embryological manipulations advancing our understanding have included the Spemann optic rudiment ablation experiments, optic vesicle transplantations as well as more contemporary work employing lineage tracers. All this has revealed that lens induction signaling is a multi-stage process involving multiple tissue interactions. More recently, molecular genetic techniques have been applied to an analysis of lens induction. This has led to the identification of signaling pathways required for lens induction and early lens development. These include the bone morphogenetic protein (Bmp) signaling pathways where Bmp4 and Bmp7 have been implicated. Though no fibroblast growth factor (Fgf) ligand has been implicated at present, the Fgf signaling pathway clearly has an important role. A series of transcription factors involved in early lens development have also been identified. These include Pax6, the Meis transcription factors, Six3, Mab21l1, FoxE3, Prox1 and Sox2. Importantly, analysis has indicated how these elements of the lens induction pathway are related and has defined genetic models to describe the process. It is a future challenge to test existing genetic models and to extend them to incorporate the tissue interactions mediated by the molecules involved. Given the complexity of this and many other developmental processes, a second century of analysis will be welcome.

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“…In normal development, the encounter between these transcription factors is determined by temporal and spatial regulation of the individual transcription factor genes, and hence by the activities of enhancers associated with each of the genes. The Pax6 lens lineage enhancer initiates Pax6 expression in a wide area of the head ectoderm starting before lens induction occurs (Williams, et al, 1998;Kammandel, et al, 1999;Xu, et al, 1999). On the other hand, Sox2 enhancer N-4 activates low-level ectodermal expression of Sox2, which itself serves as the pilot light for the occurrence of the surge of Sox2 expression induced by contact of the optic vesicle.…”

Section: Partnership Among Transcription Factors Involving Sox Proteimentioning

confidence: 99%

Interplay of Pax6 and SOX2 in lens development as a paradigm of genetic switch mechanisms for cell differentiation

Kondoh

Uchikawa²,

Kamachi³

2004

Int. J. Dev. Biol.

118

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When the cloning era arrived, our first target for cloning was the δ δ δ δ δ1-crystallin gene of the chicken, the lens-specific gene expressed earliest following lens induction. We have investigated the regulation of this gene with the idea that the mechanism of its activation must reflect that of lens differentiation per se. We here summarize the investigation carried out in our group along this line over the past 20 years. The δ δ δ δ δ1-crystallin gene is regulated by an enhancer in the third intron, and the specificity of this regulation is governed by a DNA region (called DC5) of only 30 bp DNA bound by two transcription factors. These factors have been identified as SOX1/2/3 (Group B1 SOX proteins, SOX2 being the major player) and Pax6, and have been shown to bind cooperatively to DC5 and form a ternary complex having a robust potency for transcriptional activation. In the embryo, Pax6 is widely expressed in the head ectoderm before the lens is formed, and as the optic vesicle comes into contact with the ectoderm, SOX2/3 expression is induced in the contacted area of the ectoderm, thereby allowing Pax6 and SOX2/3 to meet in the same cell nucleus, where they can then activate a battery of genes for early lens development including δ δ δ δ δ1- PreludeEye lenses are derived from head ectoderm, being induced by an effect of the optic vesicle, the retinal primordia extruding from the embryonic diencephalon. Lens develops as a remarkably transparent tissue, rich in a group of proteins collectively called crystallins. Crystallins are excellent molecular markers of lens differentiation, and have made it possible to study ectodermderived lens development as a paradigm of tissue differentiation. During the early period of modern cell differentiation studies, when cell types began to be defined on the basis of specific molecular constituents of the cells, specific anti-crystallin antibodies provided the sharpest molecular tools for the analysis of lens differentiation (Clayton and Truman, 1967;Clayton, 1970). Later, Rot analysis of crystallin cDNAs became available, and the beautiful work using this technique done by Shinohara and Piatigorsky (Shinohara and Piatigorsky, 1976) was the prelude of the real modern age of the study of lens development. Their work demonstrated that the δ1-crystallin gene is activated soon after the lens is induced in the head ectoderm by contact with the optic vesicle (retina primordium) extruding from the diencephalons. This also corroborated earlier immunochemical observations that δ1-crystallin is the first crystallin synthesized in lens development.The cloning age and δ1 δ1 δ1 δ1 δ1-crystallin regulation Then the cloning age arrived. Our first target of gene cloning was the δ1-crystallin gene of the chicken, because it was the earliest lensspecific gene to be turned on after lens induction. The idea behind this was that the mechanism of activating this gene must be deeply involved in the early process of lens differentiation, perhaps the lens induction process itself. Once th...

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A highly conserved lens transcriptional control element from the Pax-6 gene

Cited by 139 publications

References 16 publications

Genetic and epigenetic mechanisms of gene regulation during lens development

Genetic and epigenetic mechanisms of gene regulation during lens development

Pathways regulating lens induction in the mouse

Interplay of Pax6 and SOX2 in lens development as a paradigm of genetic switch mechanisms for cell differentiation

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