FGF Signaling in Chick Lens Development

Le, Anh Chi N.; Musil, Linda S.

doi:10.1006/dbio.2001.0194

Cited by 109 publications

(122 citation statements)

References 72 publications

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…4 shows that retinal cell differentiation is disrupted by these inhibitors and supports our hypothesis that the MAP kinase pathway is critical for this process. Interestingly, MEK 1͞2 inhibitor injections at earlier time points severely disrupted lens differentiation consistent with previous in vitro studies investigating the role of MAP kinase signaling on lens differentiation (32,33).…”

Section: Resultssupporting

confidence: 87%

Positional cloning of the young mutation identifies an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation

Gregg

Willer

Fadool

et al. 2003

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

View full text Add to dashboard Cite

Zebrafish with the young (yng) mutation show a defect in retinal cell differentiation. Here we demonstrate that a mutation in a brahma-related gene (brg1) is responsible for the yng phenotype. Brahma homologues function as essential subunits for SWI͞SNF-type chromatin remodeling complexes. Our analysis indicates that brg1 is required for the wave of mitogen-activated protein kinase activity that precedes retinal cell differentiation. Using specific inhibitors of the mitogen-activated protein kinase pathway we show this signal has a direct role in retinal cell differentiation. Lastly, through investigations of mutants in other chromatin remodeling subunits, we provide genetic evidence for gene and tissue specificity of the Brahma chromatin remodeling complex.zebrafish ͉ mitogen-activated protein kinase ͉ eye development

show abstract

Section: Resultssupporting

confidence: 87%

Positional cloning of the young mutation identifies an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation

Gregg

Willer

Fadool

et al. 2003

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

View full text Add to dashboard Cite

show abstract

“…Previous studies showed that FGF-1 and FGF-2 promote lens cell proliferation and lens fiber differentiation in explant cultures (4,31). Whether these two effects are achieved via identical or distinct mechanisms remains to be clarified.…”

Section: Discussionmentioning

confidence: 96%

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

View full text Add to dashboard Cite

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...

show abstract

“…7). It is important to note that ERK1/2 kinases are also downstream of insulin-mediated signaling in lens (Le and Musil, 2001). The PI3K branch of FGF-signaling associates with the complex via Gab1 that is recognized by the p85 regulatory subunit of phosphatidylinositol-3-kinase (PI3K).…”

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

confidence: 99%

Genetic and epigenetic mechanisms of gene regulation during lens development

Cvekl

Duncan

2007

Progress in Retinal and Eye Research

141

124

View full text Add to dashboard Cite

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.

show abstract

FGF Signaling in Chick Lens Development

Cited by 109 publications

References 72 publications

Positional cloning of the young mutation identifies an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation

Positional cloning of the young mutation identifies an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation

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

Genetic and epigenetic mechanisms of gene regulation during lens development

Contact Info

Product

Resources

About