PUBLICATION
Serine/threonine kinase, Melk, regulates proliferation and glial differentiation of retinal progenitor cells
- Authors
- Saito, R., Nakauchi, H., and Watanabe, S.
- ID
- ZDB-PUB-110921-1
- Date
- 2012
- Source
- Cancer science 103(1): 42-9 (Journal)
- Registered Authors
- Watanabe, Sumiko
- Keywords
- none
- MeSH Terms
-
- 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*
- PubMed
- 21923749 Full text @ Cancer Sci.
Citation
Saito, R., Nakauchi, H., and Watanabe, S. (2012) Serine/threonine kinase, Melk, regulates proliferation and glial differentiation of retinal progenitor cells. Cancer science. 103(1):42-9.
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 may 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 may play multiple roles for retinal development in vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping