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PMID:12490564

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Citation

Kubo, F, Takeichi, M and Nakagawa, S (2003) Wnt2b controls retinal cell differentiation at the ciliary marginal zone. Development 130:587-98

Abstract

The ciliary marginal zone of the vertebrate retina contains undifferentiated progenitor cells that continue to proliferate and add new neurons and glia peripherally during the embryonic stages - even after the formation of a functional retina. To understand the molecular mechanism that controls the prolonged progenitor cell proliferation in the ciliary marginal zone, we employed a candidate molecule approach, focusing on Wnt2b (formerly know as Wnt13), which is expressed in the marginal most tip of the retina. Frizzled 4 and 5, seven-pass transmembrane Wnt receptors, were expressed in the peripheral and central part of the retina, respectively. LEF1, a downstream Wnt signaling component, was expressed at high levels in the ciliary marginal zone with expression gradually decreasing towards the central retina. The LEF1-expressing region, which is where Wnt signaling is supposedly activated, expressed a set of molecular markers that are characteristic of the progenitor cells in the ciliary marginal zone. Overexpression of Wnt2b by use of in ovo electroporation in the central retina inhibited neuronal differentiation and induced the progenitor cell markers. Blocking of the Wnt downstream signaling pathway by a dominant-negative LEF1 inhibited proliferation of the cells in the marginal area, which resulted in their premature neuronal differentiation. The progenitor cells in the ciliary marginal zone differentiated into all the neuronal and glial cell types when cultured in vitro, and they proliferated for a longer period than did centrally located progenitor cells that underwent a limited number of cell divisions. In addition, the proliferation of these progenitor cells was promoted in the presence of Wnt2b. These results suggest that Wnt2b functions to maintain undifferentiated progenitor cells in the ciliary marginal zone, and thus serves as a putative stem cell factor in the retina.

Links

PubMed

Keywords

Animals; Avian Proteins; Cell Differentiation; Chick Embryo; Ciliary Body/embryology; DNA-Binding Proteins/genetics; Gene Expression Regulation, Developmental; Iris/embryology; Lymphoid Enhancer-Binding Factor 1; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology; RNA, Messenger/genetics; RNA, Messenger/metabolism; Retina/embryology; Retinal Ganglion Cells/cytology; Retinal Ganglion Cells/metabolism; Signal Transduction; Stem Cells/cytology; Stem Cells/metabolism; Transcription Factors/genetics; Wnt2 Protein

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CHICK:O42486

located_in

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:O93345

involved_in

GO:0008283: cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

MOUSE:FZD4

enables

GO:0017147: Wnt-protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q98SN7

F

Seeded From UniProt

complete

CHICK:WNT2B

involved_in

GO:0008283: cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000540)

Seeded From UniProt

complete

CHICK:O42486

part_of

GO:0016020: membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:O93345

involved_in

GO:0008283: cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:O93345

involved_in

GO:0045665: negative regulation of neuron differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:WNT2B

involved_in

GO:0045665: negative regulation of neuron differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:WNT2B

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:WNT2B

involved_in

GO:0008283: cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:WNT2B

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q61088

F

Seeded From UniProt

complete

CHICK:WNT2B

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13467

F

Seeded From UniProt

complete

CHICK:Q9PUI3

involved_in

GO:0045665: negative regulation of neuron differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q9PUI3

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q9PUI3

involved_in

GO:0008283: cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q9PUI3

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q61088

F

Seeded From UniProt

complete

CHICK:Q9PUI3

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13467

F

Seeded From UniProt

complete

HUMAN:FZD5

enables

GO:0017147: Wnt-protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q98SN7

F

Seeded From UniProt

complete


See also

References

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