Excess lunatic fringe causes cranial neural crest over-proliferation.
Lunatic fringe is a vertebrate homologue of Drosophila fringe, which plays an important role in modulating Notch signaling. This study examines the distribution of chick lunatic fringe at sites of neural crest formation and explores its possible function by ectopic expression. Shortly after neural tube closure, lunatic fringe is expressed in most of the neural tube, with the exception of the dorsal midline containing presumptive neural crest. Thus, there is a fringe/non-fringe border at the site of neural crest production. Expression of excess lunatic fringe in the cranial neural tube and neural crest by retrovirally mediated gene transfer resulted in a significant increase ( approximately 60%) in the percentage of cranial neural crest cells 1 day after infection. This effect was mediated by an increase in cell division as assayed by BrdU incorporation. Infected embryos had an up-regulation of Delta-1 in the dorsal neural tube and redistribution of Notch-1 to the lumen of the neural tube, confirming that excess fringe modulates Notch signaling. These findings point to a novel role for lunatic fringe in regulating cell division and/or production of neural crest cells by the neural tube.
Nellemann
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Division of Biology, California Institute of Technology 139-74, Pasadena, California 91125, USA.
de Bellard
M E
ME
Barembaum
M
M
Laufer
E
E
Bronner-Fraser
M
M
D000818:Animals; D030161:Avian Proteins; D002455:Cell Division / Q000502:physiology*; D002642:Chick Embryo; D016695:Glycosyltransferases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology*; D011506:Proteins / Q000502:physiology*; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D012886:Skull / Q000166:cytology / Q000196:embryology*; D014157:Transcription Factors
D030161:Avian Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; C064045:delta protein; D016695:Glycosyltransferases; C498394:LFNG protein, Gallus gallus