Cell cycle regulation in the developing lens

Griep, Anne E.

doi:10.1016/j.semcdb.2006.10.004

Cited by 51 publications

(43 citation statements)

References 157 publications

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“…Similarly, the extremely high levels of accumulation of GAD at the anterior and posterior lens poles and the conspicuous "patchy" GAD staining in the central lens epithelium during E13.5-E16.5 suggests that GAD/GABA are involved in cell adhesion mechanisms between fibers of opposite sides during formation of lens sutures (Beebe et al, 2001). The striking epithelial expression of GAD may also correspond to the two proliferative zones described earlier (for review, see Griep, 2006), a possibility that needs to be verified. The highest level of expression of both EGAD and GAD65 was observed in the primary lens fibers at stages 16.5-E17.5 characterized by extensive fiber elongation and beginning of nuclear disintegration.…”

Section: Sequential Induction and Spatial Segregation Of Different Gamentioning

confidence: 67%

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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Section: Sequential Induction and Spatial Segregation Of Different Gamentioning

confidence: 67%

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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“…Cell cycle exit, signaling and lens-specific proteins-Lens differentiation commences as soon as the lens vesicle, comprised of a single layer of cuboidal epithelial cells, pinches off from the surface ectoderm. The lens vesicle is polarized with its anterior cells retaining their epithelial morphology and proliferative capacity, whereas the posterior lens precursor cells exit the cell cycle (see Griep, 2006) and initiate terminal differentiation forming the primary lens fibers. Cell cycle exit is linked to the upregulation of p57 Kip2 and pRb, and downregulation of E2Fs and cyclin B1 (see Griep, 2006).…”

Section: Lens Fiber Cell Differentiationmentioning

confidence: 99%

“…The lens vesicle is polarized with its anterior cells retaining their epithelial morphology and proliferative capacity, whereas the posterior lens precursor cells exit the cell cycle (see Griep, 2006) and initiate terminal differentiation forming the primary lens fibers. Cell cycle exit is linked to the upregulation of p57 Kip2 and pRb, and downregulation of E2Fs and cyclin B1 (see Griep, 2006). Lens differentiation is regulated by secreted growth factors including members of the FGF family originating from the prospective retina (see Lovicu and McAvoy, 2005;Robinson, 2006).…”

Section: Lens Fiber Cell Differentiationmentioning

confidence: 99%

“…FGF signaling also stimulates both cell cycle exit (see Griep, 2006) and the lens differentiation program via the upregulation of crystallin gene expression. Identification of individual FGFs and their receptors controlling distinct phases of lens development is hampered by a wide repertoire of functional redundancies and compensatory effects (see Robinson, 2006).…”

Section: Fgf Signaling In Lens Differentiation-a Schematic Diagram Ofmentioning

confidence: 99%

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Genetic and epigenetic mechanisms of gene regulation during lens development

Cvekl

Duncan

2007

Progress in Retinal and Eye Research

141

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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“…Lens stem cells are thought to reside in the germinative zone, although recent work has shown that the central epithelial cells may be the site of lens stem cells (Griep, 2006;Zhou et al, 2006). Very recently, it has been hypothesized that lens stem cells may reside in the ciliary body (Remington and Meyer, 2007).…”

Section: Biological Origins Of Lens Epithelial Cellsmentioning

confidence: 99%

The lens epithelium: Focus on the expression and function of the α-crystallin chaperones

Andley

2008

The International Journal of Biochemistry & Cell Biology

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Lens epithelial cells are the parental cells responsible for growth and development of the transparent ocular lens. Many elegant investigations into their biology have focused on the factors that initiate and regulate lens epithelial cell differentiation. Because they serve key transport and cell maintenance functions throughout life, and are the primary source of metabolic activity in the lens, mechanisms to maintain lens epithelial cell integrity and survival are critical for lens transparency. The molecular chaperones α-crystallins are abundant proteins synthesized in the differentiated lens fiber cell cytoplasm. However, their expression in lens epithelial cells has only been appreciated very recently. Besides their important roles in the refractive and light focusing properties of the lens, α-crystallins have been implicated in a number of non-refractive pathways including those involving stress response, apoptosis and cell survival. The most convincing evidence for their importance in the lens epithelium has been shown by studies on the properties of lens epithelial cells from αA and αB-crystallin gene knockout mice. The effective combination of genetics, cell and molecular biology possible with lens epithelial cells is attracting an increasing number of researchers focused on understanding how lens epithelial cells coordinate survival, proliferation and differentiation. Cell facts• Lens epithelial cells are responsible for the growth and development of the entire ocular lens • Lens development is controlled by cell cycle regulators, signaling molecules and growth factors such as FGF • Lens epithelial cells express members of the small heat shock protein family of molecular chaperones, αA and βB-crystallins, the first crystallins to be expressed during lens development • α-Crystallins likely protect lens epithelial cells from environmental stress throughout life, and thus may delay the onset of age-related cataract • Lens epithelial cell proliferation is deregulated in posterior capsule opacification leading to secondary cataract, a complication in up to 50% of cataract surgeries Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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Cell cycle regulation in the developing lens

Cited by 51 publications

References 157 publications

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

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

Genetic and epigenetic mechanisms of gene regulation during lens development

The lens epithelium: Focus on the expression and function of the α-crystallin chaperones

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