Chicken embryo lens cultures mimic differentiation in the lens

Menko, A. Sue; Klukas, Kathleen A.; Johnson, Ross G.

doi:10.1016/0012-1606(84)90014-9

Cited by 112 publications

(101 citation statements)

References 26 publications

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“…In earlier studies from this laboratory, we showed that the initiation of lens cell differentiation in culture is characterized by cell compaction, resulting in a monolayer of tightly packed epithelial cells (Menko et al, 1984). This process is accompanied by localization of N-cadherin to cell-cell interfaces and reorganization of filamentous actin from stress fibers to a cortical distribution (Ferreira-Cornwell et al, 2000).…”

Section: Introductionmentioning

confidence: 87%

“…As they begin to differentiate, these lens cells compact, appearing as a monolayer of cuboidal shaped epithelial cells and then go on to form differentiated lentoid bodies (data not shown). We previously demonstrated that cell compaction is correlated with the initiation of lens cell differentiation (Menko et al, 1984). The timing of these morphogenetic changes was unaffected by exposure to PP3.…”

Section: Compaction Of the Lens Epithelial Cell Monolayer In Responsementioning

confidence: 95%

“…The presence of distinct zones of proliferation and differentiation has made the embryonic lens a valuable model in the study of molecular changes associated with cell proliferation and cell cycle withdrawal (Harris et al, 1992;Rinaudo and Zelenka, 1992;Rampalli et al, 1998;Lovicu and McAvoy, 1999). Similar to lens development in vivo, lens epithelial cells grown in culture first proliferate and then withdraw from the cell cycle before they begin their differentiation (Menko et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

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Transition between proliferation and differentiation for lens epithelial cells is regulated by Src family kinases

Walker

Zhang

Menko

2002

Developmental Dynamics

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As in many cell types, lens cells must withdraw from the cell cycle before they initiate their differentiation. The involvement of Src family kinases (SFKs) in this key initiating event in cell differentiation was examined in lens epithelial cell cultures. SFK activity was suppressed with the specific inhibitor PP1. This induced expression of the cyclin-dependent kinase (CDK) inhibitors p27 and p57 and suppressed lens epithelial cell proliferation. Therefore, inhibition of SFK activity created conditions permissive for undifferentiated lens epithelial cells to withdraw from the cell cycle. Growth of the lens epithelial cell cultures in the presence of PP1 induced expression of filensin and CP49, lens differentiation-specific intermediate filament proteins, providing evidence that suppression of SFK activity also promoted the initiation of lens cell differentiation. The mechanism by which PP1 signaled cell cycle withdrawal and commitment to differentiation was shown to involve induction of N-cadherin cell-cell junction assembly and reorganization of the actin cytoskeleton from stress fibers to cortical filaments. This result was supported by the compaction of the epithelial monolayer in response to PP1, a morphogenetic change that we have previously shown to be dependent on N-cadherin function and a hallmark of the commencement of the lens differentiation program in culture. The results presented in this study suggest that the decision of lens epithelial cells to withdraw from the cell cycle and initiate differentiation requires inhibition of SFKs and the formation of N-cadherin cell-cell junctions.

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Section: Introductionmentioning

confidence: 87%

Section: Compaction Of the Lens Epithelial Cell Monolayer In Responsementioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Transition between proliferation and differentiation for lens epithelial cells is regulated by Src family kinases

Walker

Zhang

Menko

2002

Developmental Dynamics

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“…L-Maf protein was not detected in untreated control lens cells but was detected in the PD98059-treated cells (Fig. 6E) (29,30), which appear to contain a few different cell types (30). Relatively large fiber cells in the central region of the lentoid bodies are surrounded by small cells, suggesting that the central cells are differentiated into fiber cells, whereas the edge cells remains undifferentiated.…”

Section: Regulation Of L-maf By Fgf-2/erk In Lens Differentiationmentioning

confidence: 93%

The Stability of the Lens-specific Maf Protein is Regulated by Fibroblast Growth Factor (FGF)/ERK Signaling in Lens Fiber Differentiation

Ochi

Ogino²,

Kageyama

et al. 2003

Journal of Biological Chemistry

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Fibroblast growth factor (FGF) signaling is necessary for both proliferation and differentiation of lens cells. However, the molecular mechanisms by which FGFs exert their effects on the lens remain poorly understood. In this study, we show that FGF-2 repressed the expression of lens-specific genes at the proliferative phase in primary cultured lens cells. Using transfected cells, we also found that the activity of L-Maf, a lens differentiation factor, is repressed by FGF/ERK signaling. L-Maf is shown to be phosphorylated by ERK, and introduction of mutations into the ERK target sites on L-Maf promotes its stabilization. The stable L-Maf mutant protein promotes the differentiation of lens cells from neural retina cells. Taken together, these results indicate that FGF/ERK signaling negatively regulates the function of L-Maf in proliferative lens cells and that stabilization of the L-Maf protein is important for lens fiber differentiation.The vertebrate lens consists of only two cell populations, and because of this simple tissue organization, it provides an excellent model of cell differentiation. The anterior surface of the lens is covered by a simple epithelium, whereas the remainder and bulk of the lens is composed of elongated lens fibers (1). During embryonic development and throughout the life of the organism, fiber cells are added via differentiation of the lens epithelial cells. The proliferative epithelial cells in the anterior germinative zone move across the lens equator to the posterior transitional zone followed by withdrawal of cell cycling and differentiation into fiber cells. Fiber cell differentiation is characterized by cell elongation and the eventual degradation of all cellular organelles including the nucleus. (7), and a secreted form of FGFR can cause a delay in fiber differentiation (9). Together, these studies implicate FGFs as bifunctional molecules that regulate both proliferation and differentiation of the lens cells. The transcription factors that mediate FGF signaling in lens development and the molecular mechanisms used by FGFs to regulate the transcriptional factors remain to be identified. Several transcription factors, including Pax6, Sox2, Six3, c-Maf, and L-Maf, are known to be important in lens development and in regulating the expression of lens-specific genes such as crystallin genes (10 -17). Of these factors, L-Maf is one of the most attractive candidates for mediating FGF signaling, because L-Maf has been identified as a lens-specific regulator of avian ␣A-crystallin expression (14), and c-maf-deficient mice have defective lens fiber differentiation and loss of crystallin gene expression (16, 17). There results show that Mafs are critical for expression of crystallin genes and lens fiber differentiation. L-Maf is a basic region/leucine zipper transcription factor and regulates the expression of ␣A-crystallin by binding the lens-specific enhancer element ␣CE2 (14, 18). In chicken, the expression of L-maf is initiated in the lens placode and is subsequently restricted to th...

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“…We further confirmed the localization of Equarin protein in lens cells. In primary embryonic chick lens dissociated cellderived monolayer (DCDML) cultures, lens cells form a cuboidal packed epithelium when they begin to differentiate (Menko et al, 1984). At this stage, Equarin protein was localized in the extracellular region of the lens cells and cell-cell borders ( Fig.…”

Section: Localization Of Equarin Protein In Chick Lens Cellsmentioning

confidence: 99%

Equarin is involved in cell adhesion by means of heparan sulfate proteoglycan during lens development

Song

Sato

Sekiguchi

et al. 2012

Developmental Dynamics

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Background: Adhesion molecules are known to be instructive for both development and differentiation. During lens differentiation, epithelial cells undergo vertical elongation, with the anterior and posterior tips of the elongating fiber cells sliding along the epithelium and capsule, respectively. These cellular processes are highly coordinated through cell adhesive interactions, actin cytoskeletal reorganization and contractile force generation. Alterations in extracellular matrix composition that interfere with these interactions can lead to defects that alter tissue morphogenesis and the state of differentiation. We have demonstrated that Equarin, which is a secreted molecule expressed in the equator region of the lens, plays an important role in chick lens fiber differentiation through fibroblast growth factor signaling. Results: Here, we explored the function of Equarin in chick lens cell adhesion. Equarin protein was expressed in the extracellular region of lens differentiating cells. We found that Equarin promoted lens cell adhesion through heparan sulfate proteoglycan. By biochemical analysis, we found that Equarin directly binds syndecan-3, which displayed a similar expression pattern to Equarin. Overexpression of Equarin resulted in altered actin localization. Conclusions: Equarin is involved in cell adhesion during fiber differentiation and development. Developmental Dynamics 242:23-29,

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Chicken embryo lens cultures mimic differentiation in the lens

Cited by 112 publications

References 26 publications

Transition between proliferation and differentiation for lens epithelial cells is regulated by Src family kinases

Transition between proliferation and differentiation for lens epithelial cells is regulated by Src family kinases

The Stability of the Lens-specific Maf Protein is Regulated by Fibroblast Growth Factor (FGF)/ERK Signaling in Lens Fiber Differentiation

Equarin is involved in cell adhesion by means of heparan sulfate proteoglycan during lens development

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