RRC ID 17638
著者 Saito R, Nakauchi H, Watanabe S.
タイトル Serine/threonine kinase, Melk, regulates proliferation and glial differentiation of retinal progenitor cells.
ジャーナル Cancer Sci
Abstract Serine/threonine kinase, Melk, was initially cloned in oocytes, but it is expressed in normal tissues and especially in cancer cells. We had previously identified Melk as a gene that is highly expressed in immature mouse retinal progenitors. To analyze the function of Melk in embryogenesis, we cloned zebrafish Melk and reported that morpholino-based downregulation of Melk in zebrafish resulted in severe anemia. Melk-morpholino-treated zebrafish also showed microphthalmia, suggesting the participation of Melk in retinal development. In Melk-depleted retinas, differentiation of retinal neurons took place but was delayed, and the proliferative period of retinal progenitor cells was prolonged, suggesting that Melk might regulate the timing of the transition from proliferation to differentiation. For more detailed examination, we performed gain- and loss-of-function analyses of Melk in mouse retinas. Knockdown of Melk by shRNA in mouse embryonic retinal explant culture resulted in decreased proliferative activity of retinal progenitors, and accordingly, overexpression of Melk slightly enhanced proliferation. Differentiation of retinal progenitor into subtypes of retinal neurons was not significantly affected, but Müller glia differentiation was perturbed by the level of Melk. Furthermore, process extension of glial cells was enhanced in the absence of Melk, suggesting that Melk is involved in the morphological differentiation of retinal cells. Taken together, our results suggest that Melk is primarily required for proper proliferation, and might play multiple roles in retinal development in vertebrates.
巻・号 103(1)
ページ 42-9
公開日 2012-1-1
DOI 10.1111/j.1349-7006.2011.02104.x
PMID 21923749
MeSH Animals Blotting, Western Cell Differentiation* Cell Proliferation* Cells, Cultured Embryo, Nonmammalian / cytology Embryo, Nonmammalian / metabolism Eye / growth & development Eye / metabolism Eye / pathology Gene Expression Regulation, Developmental In Situ Hybridization Mice Neuroglia / cytology* Neuroglia / metabolism Neurons / cytology Neurons / metabolism Oligodeoxyribonucleotides, Antisense / pharmacology Protein Serine-Threonine Kinases / antagonists & inhibitors Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* RNA Probes RNA, Messenger / genetics Retina / cytology* Retina / embryology Retina / metabolism Reverse Transcriptase Polymerase Chain Reaction Stem Cells / cytology* Stem Cells / metabolism Zebrafish / embryology Zebrafish / metabolism*
IF 4.966
引用数 12
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 Y79(RCB1645)