The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in Xenopus laevis.
BACKGROUND
The neural crest is a unique population of cells that arise in the vertebrate ectoderm at the neural plate border after which they migrate extensively throughout the embryo, giving rise to a wide range of derivatives. A number of proteins involved in neural crest development have dynamic expression patterns, and it is becoming clear that ubiquitin-mediated protein degradation is partly responsible for this.


RESULTS
Here we demonstrate a novel role for the F-box protein Cdc4/Fbxw7 in neural crest development. Two isoforms of Xenopus laevis Cdc4 were identified, and designated xCdc4alpha and xCdc4beta. These are highly conserved with vertebrate Cdc4 orthologs, and the Xenopus proteins are functionally equivalent in terms of their ability to degrade Cyclin E, an established vertebrate Cdc4 target. Blocking xCdc4 function specifically inhibited neural crest development at an early stage, prior to expression of c-Myc, Snail2 and Snail.


CONCLUSIONS
We demonstrate that Cdc4, an ubiquitin E3 ligase subunit previously identified as targeting primarily cell cycle regulators for proteolysis, has additional roles in control of formation of the neural crest. Hence, we identify Cdc4 as a protein with separable but complementary functions in control of cell proliferation and differentiation.
Almeida
Alexandra D
AD
Department of Oncology, University of Cambridge, Hutchison-MRC Research Centre, Addenbrookes Hospital, Hills Road, Cambridge, CB2 0XZ, UK.
Wise
Helen M
HM
Hindley
Christopher J
CJ
Slevin
Michael K
MK
Hartley
Rebecca S
RS
Philpott
Anna
A
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D019927:Cyclin E / Q000378:metabolism; D018076:DNA, Complementary; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008845:Microinjections; D009432:Neural Crest / Q000196:embryology* / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger; D017384:Sequence Deletion; D025801:Ubiquitin / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
D019927:Cyclin E; D018076:DNA, Complementary; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C549199:Fbxw7 protein, Xenopus; D020033:Protein Isoforms; D012333:RNA, Messenger; D025801:Ubiquitin; D029867:Xenopus Proteins