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PMID:23111152

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Citation

Luo, J, Uribe, RA, Hayton, S, Calinescu, AA, Gross, JM and Hitchcock, PF (2012) Midkine-A functions upstream of Id2a to regulate cell cycle kinetics in the developing vertebrate retina. Neural Dev 7:33

Abstract

ABSTRACT: BACKGROUND: Midkine is a small heparin binding growth factor expressed in numerous tissues during development. The unique midkine gene in mammals has two paralogs in zebrafish: midkine-a (mdka) and midkine-b (mdkb). In the zebrafish retina, during both larval development and adult photoreceptor regeneration, mdka is expressed in retinal stem and progenitor cells and functions as a molecular component of the retina's stem cell niche. In this study, loss-of-function and conditional overexpression were used to investigate the function of Mdka in the retina of the embryonic zebrafish. RESULTS: The results show that during early retinal development Mdka functions to regulate cell cycle kinetics. Following targeted knockdown of Mdka synthesis, retinal progenitors cycle more slowly, and this results in microphthalmia, a diminished rate of cell cycle exit and a temporal delay of cell cycle exit and neuronal differentiation. In contrast, Mdka overexpression results in acceleration of the cell cycle and retinal overgrowth. Mdka gain-of-function, however, does not temporally advance cell cycle exit. Experiments to identify a potential Mdka signaling pathway show that Mdka functions upstream of the HLH regulatory protein, Id2a. Gene expression analysis shows Mdka regulates id2a expression, and co-injection of Mdka morpholinos and id2a mRNA rescues the Mdka loss-of-function phenotype. CONCLUSIONS: These data show that in zebrafish, Mdka resides in a shared Id2a pathway to regulate cell cycle kinetics in retinal progenitors. This is the first study to demonstrate the function of Midkine during retinal development and adds Midkine to the list of growth factors that transcriptionally regulate Id proteins.

Links

PubMed Online version:10.1186/1749-8104-7-33

Keywords


Significance

Annotations

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

DANRE:A0A0B5JQ06

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-050531-5

P

Seeded From UniProt

complete

DANRE:A0A0B5JQ06

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-130416-1

P

Seeded From UniProt

complete

DANRE:A0A1D5NS41

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-050531-5

P

Seeded From UniProt

complete

DANRE:A0A1D5NS41

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-130416-1

P

Seeded From UniProt

complete

DANRE:A0A1D5NST4

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-050531-5

P

Seeded From UniProt

complete

DANRE:A0A1D5NST4

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-130416-1

P

Seeded From UniProt

complete

DANRE:A0A1D5NSV1

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-050531-5

P

Seeded From UniProt

complete

DANRE:A0A1D5NSV1

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-130416-1

P

Seeded From UniProt

complete

DANRE:E9QIK2

GO:0051726: regulation of cell cycle

ECO:0000315:

P

Figure 3(A)(c) shows that in the absence of Mdka, "central retinal progenitors fail to exit the cell cycle at the appropriate developmental stage," implying that "Mdka functions to control cell cycle kinetics."

complete
CACAO 5682

DANRE:E9QIK2

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-130416-1

P

Seeded From UniProt

complete

DANRE:E9QIK2

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-050531-5

P

Seeded From UniProt

complete

DANRE:E9QIK2

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:Q9W767

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-130416-1

P

Seeded From UniProt

complete

DANRE:Q9W767

involved_in

GO:0051726: regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-050531-5

P

Seeded From UniProt

complete


See also

References

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