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PMID:21220025

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Citation

Fukuda, T, Tokunaga, A, Sakamoto, R and Yoshida, N (2011) Fbxl10/Kdm2b deficiency accelerates neural progenitor cell death and leads to exencephaly. Mol. Cell. Neurosci. 46:614-24

Abstract

Histone methylation is the important transcription regulatory system that affects mammalian development and cell differentiation. Alterations in epigenetic gene regulation are associated with disease. Fbxl10 (F-box and leucine-rich repeat protein 10) is a JmjC domain-containing histone demethylase. Although Fbxl10 has been implicated in cell cycle regulation, cell death, senescence, and tumorigenesis, these functions are controversial and its physiological function is unclear. To determine the in vivo function of Fbxl10, in this study, we generated a homozygous mutation in the mouse Fbxl10 gene. About half of Fbxl10-deficient mice exhibit failure of neural tube closure, resulting in exencephaly and die shortly after birth. Fbxl10 deficiency also causes retinal coloboma and a curled tail with low penetrances. Fbxl10 mRNA is specifically expressed in the cranial neural folds at E8.5 embryos, and apoptosis increased in the neuroepithelium and mesenchyme of Fbxl10-deficient E9.5 embryos, consistent with neural tube defects found in Fbxl10-deficient mice. Depletion of Fbxl10 induced the increased expression of p19ARF, an inducer of apoptosis, in E8.5 embryos and mouse embryonic fibroblast cells. In addition, the number of mitotic neural progenitor cells is significantly increased in the mutant E14.5 brain. Our findings suggest that the Fbxl10 gene makes important contributions to embryonic neural development by regulating cell proliferation and cell death in mice.

Links

PubMed Online version:10.1016/j.mcn.2011.01.001

Keywords

Animals; Cell Death/physiology; Cell Differentiation; Cell Proliferation; Embryo, Mammalian/abnormalities; Embryo, Mammalian/anatomy & histology; Embryo, Mammalian/metabolism; Embryo, Mammalian/physiology; F-Box Proteins/genetics; Female; Gene Expression Regulation, Developmental; Humans; Jumonji Domain-Containing Histone Demethylases/deficiency; Jumonji Domain-Containing Histone Demethylases/genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Crest; Neural Stem Cells/cytology; Neural Stem Cells/physiology; Neural Tube Defects/embryology; Neural Tube Defects/genetics; Neural Tube Defects/pathology; Neural Tube Defects/physiopathology

Significance

Annotations

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

MOUSE:KDM2B

enables

GO:0032452: histone demethylase activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0021993: initiation of neural tube closure

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0021678: third ventricle development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0021670: lateral ventricle development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0021592: fourth ventricle development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0021555: midbrain-hindbrain boundary morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0007283: spermatogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0030902: hindbrain development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0030901: midbrain development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0030900: forebrain development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0048596: embryonic camera-type eye morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:2000178: negative regulation of neural precursor cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM2B

involved_in

GO:0043524: negative regulation of neuron apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KDM2B

enables

GO:0032452: histone demethylase activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete


See also

References

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