Xenopus NM23-X4 regulates retinal gliogenesis through interaction with p27Xic1.
BACKGROUND
In Xenopus retinogenesis, p27Xic1, a Xenopus cyclin dependent kinase inhibitor, functions as a cell fate determinant in both gliogenesis and neurogenesis in a context dependent manner. This activity is essential for co-ordination of determination and cell cycle regulation. However, very little is known about the mechanism regulating the context dependent choice between gliogenesis versus neurogenesis.


RESULTS
We have identified NM23-X4, a NM23 family member, as a binding partner of p27Xic1. NM23-X4 is expressed at the periphery of the ciliary marginal zone of the Xenopus retina and the expression overlaps with p27Xic1 at the central side. Our in vivo functional analysis in Xenopus retina has shown that knockdown of NM23-X4 activates gliogenesis. Furthermore, co-overexpression of NM23-X4 with p27Xic1 results in the inhibition of p27Xic1-mediated gliogenesis, through direct interaction of NM23-X4 with the amino-terminal side of p27Xic1. This inhibitory effect on gliogenesis requires serine-150 and histidine-148, which correspond to the important residues for the kinase activities of NM23 family members.


CONCLUSIONS
This study demonstrates that NM23-X4 functions as an inhibitor of p27Xic1-mediated gliogenesis in Xenopus retina and suggests that this activity contributes to the proper spatio-temporal regulation of gliogenesis.
Mochizuki
Toshiaki
T
Hutchison/MRC Research Centre, Department of Oncology, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK. full-moon@umin.ac.jp
Bilitou
Aikaterini
A
Waters
Caroline T
CT
Hussain
Kamran
K
Zollo
Massimo
M
Ohnuma
Shin-ichi
S
D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014981:Xenopus / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D029867:Xenopus Proteins; C493963:Xicl protein, Xenopus; D050760:Cyclin-Dependent Kinase Inhibitor p27