Lentropin, a protein that controls lens fiber formation, is related functionally and immunologically to the insulin-like growth factors.

Beebe, David C.; Silver, Michael H.; Belcher, Karla S.; Wyk, Judson J. Van; Svoboda, Marjorie E.; Zelenka, Peggy S.

doi:10.1073/pnas.84.8.2327

Cited by 132 publications

(57 citation statements)

References 31 publications

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“…FGFs, IGF-1 and BMPs have been implicated as factors that stimulate fiber cell differentiation in cultured explants in vitro (Beebe et al, 1987;Chamberlain and McAvoy, 1987;Peek et al, 1992;Belecky-Adams et al, 2002). Although FGFs, IGF-1 and BMPs play important roles in the lens developmental processes, these factors may not be sufficient for the full differentiation of lens fiber cells.…”

Section: Discussionmentioning

confidence: 99%

Wnt signaling enhances FGF2-triggered lens fiber cell differentiation

Lyu

Joo

2004

Development

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Wnt signaling is implicated in many developmental processes, including cell fate changes. Several members of the Wnt family, as well as other molecules involved in Wnt signaling, including Frizzled receptors, LDL-related protein co-receptors, members of the Dishevelled and Dickkopf families, are known to be expressed in the lens during embryonic or postembryonic development. However, the function of Wnt signaling in lens fiber differentiation remains unknown. Here, we show that GSK-3β kinase is inactivated and that β-catenin accumulates during the early stages of lens fiber cell differentiation. In an explant culture system, Wnt conditioned medium (CM) induced the accumulation of β-crystallin, a marker of fiber cell differentiation, without changing cell shape. In contrast, epithelial cells stimulated with Wnt after priming with FGF elongated, accumulated β-crystallin, aquaporin-0, p57kip2, and altered their expression of cadherins. Treatment with lithium, which stabilizes β-catenin, induced the accumulation of β-crystallin, but explants treated with lithium after FGF priming did not elongate as they did after Wnt application. These results show that Wnts promote the morphological aspects of fiber cell differentiation in a process that requires FGF signaling, but is independent of β-catenin. Wnt signaling may play an important role in lens epithelial-tofiber differentiation.

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Section: Discussionmentioning

confidence: 99%

Wnt signaling enhances FGF2-triggered lens fiber cell differentiation

Lyu

Joo

2004

Development

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“…Although the precise identity of these factors remains unknown, a number of previously characterized growth factors and hormones have been shown to promote proliferation and differentiation of lens cells in vitro (Piatigorsky 1973;Beebe et al 1987;Chamberlain and McAvoy 1987;Brewitt and Clark 1988). These include insulin and insulin-like growth factor-I (IGF-I), whose activity has been identified in chicken vitreous humor (Beebe et al 1987). Presently, it is not known whether these signals are operational in vivo.…”

Section: Retinoids and Their Role In Lens Developmentmentioning

confidence: 99%

“…Factors stimulating proliferation and differentiation of lens cells in culture have been identified in extracts from ocular tissues, including the retina and vitreous humor (Arruti and Courtois 1978;Barritault et al 1981;Beebe et al 1987). Although the precise identity of these factors remains unknown, a number of previously characterized growth factors and hormones have been shown to promote proliferation and differentiation of lens cells in vitro (Piatigorsky 1973;Beebe et al 1987;Chamberlain and McAvoy 1987;Brewitt and Clark 1988). These include insulin and insulin-like growth factor-I (IGF-I), whose activity has been identified in chicken vitreous humor (Beebe et al 1987).…”

Section: Retinoids and Their Role In Lens Developmentmentioning

confidence: 99%

“…During thelial cells differentiate into fiber cells in response to factors secreted from the retina (Coulombre and Cou o lombre 1963;Yamamoto 1976;Reyer 1977}. Although a number of hormones and growth factors have been shown to influence growth and differentiation of lens cells in culture (Piatigorsky 1973; Beebe et al 1987; Chamberlain and McAvoy 1987;Brewitt and Clark 1988}, it is not known what signals are required in vivo. Thus, the 7-crystallin genes provide an excellent opportunity to investigate the molecules and mechanisms that regulate differentiation during lens development.…”

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confidence: 99%

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An everted repeat mediates retinoic acid induction of the gamma F-crystallin gene: evidence of a direct role for retinoids in lens development.

Tini¹,

Otulakowski²,

Breitman³

et al. 1993

Genes Dev.

156

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The vertebrate lens is a classical system for examining mechanisms of tissue determination and differentiation, yet little is known about the signaling molecules controlling its development. Here, we report that retinoic acid IRA}, a substance known for its teratogenic effects on the eye and as a natural endogenous morphogenetic agent, acts as a regulator of gene expression in the lens. We have identified a novel type of RA response element (RARE) within the lens-specific mouse 7F-crystallin promoter, consisting of two (A/G)GGTCA motifs in an everted arrangement spaced by 8 nucleotides. This element {TF-RARE) mediates activation of the 7F-crystallin promoter by ligand-activated endogenous lens cell RA receptors (RARs) and confers RA responsiveness when linked to a heterologous promoter. 7F-RARE is bound in vitro by RAR/RXR heterodimers, and both receptors cooperate in vivo to trans-activate this element. These observations demonstrate a direct effect of RA on lens-specific gene expression and reveal a novel role for retinoids in the development and homeostasis of the mammalian eye.

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“…The vitreous humor contains numerous growth factors that activate specific receptor tyrosine kinases (RTKs) present on lens epithelial cells. These growth factors include: insulin-like growth factor (IGF) (Beebe et al, 1987), platelet-derived growth factor (PDGF) (Cassidy et al, 1998), epidermal growth factor (EGF) (Majima, 1997), hepatocyte growth factor (HGF) (Katsura et al, 1998), vascular endothelial growth factor (VEGF) (Shui et al, 2003) and fibroblast growth factor (FGF) (McAvoy and Chamberlain, 1990). Binding of any of these growth factors to their specific RTKs induces the activation of Ras/Erk and PI3-K/Akt signaling pathways in lens epithelial cells (Iyengar et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Frs2α enhances fibroblast growth factor-mediated survival and differentiation in lens development

et al. 2012

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SUMMARYMost growth factor receptor tyrosine kinases (RTKs) signal through similar intracellular pathways, but they often have divergent biological effects. Therefore, elucidating the mechanism of channeling the intracellular effect of RTK stimulation to facilitate specific biological responses represents a fundamental biological challenge. Lens epithelial cells express numerous RTKs with the ability to initiate the phosphorylation (activation) of Erk1/2 and PI3-K/Akt signaling. However, only Fgfr stimulation leads to lens fiber cell differentiation in the developing mammalian embryo. Additionally, within the lens, only Fgfrs activate the signal transduction molecule Frs2. Loss of Frs2 in the lens significantly increases apoptosis and decreases phosphorylation of both Erk1/2 and Akt. Also, Frs2 deficiency decreases the expression of several proteins characteristic of lens fiber cell differentiation, including Prox1, p57 KIP2 , aquaporin 0 and -crystallins. Although not normally expressed in the lens, the RTK TrkC phosphorylates Frs2 in response to binding the ligand NT3. Transgenic lens epithelial cells expressing both TrkC and NT3 exhibit several features characteristic of lens fiber cells. These include elongation, increased Erk1/2 and Akt phosphorylation, and the expression of -crystallins. All these characteristics of NT3-TrkC transgenic lens epithelial cells depend on Frs2. Therefore, tyrosine phosphorylation of Frs2 mediates Fgfr-dependent lens cell survival and provides a mechanistic basis for the unique fiber-differentiating capacity of Fgfs on mammalian lens epithelial cells.

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Lentropin, a protein that controls lens fiber formation, is related functionally and immunologically to the insulin-like growth factors.

Cited by 132 publications

References 31 publications

Wnt signaling enhances FGF2-triggered lens fiber cell differentiation

Wnt signaling enhances FGF2-triggered lens fiber cell differentiation

An everted repeat mediates retinoic acid induction of the gamma F-crystallin gene: evidence of a direct role for retinoids in lens development.

Frs2α enhances fibroblast growth factor-mediated survival and differentiation in lens development

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