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 di stribution of chick lunatic fringe at sites of neural crest formation and e xplores its possible function by ectopic expression. Shortly after neural t ube closure, lunatic fringe is expressed in most of the neural tube, with t he exception of the dorsal midline containing presumptive neural crest. Thu s, there is a fringe/non-fringe border at the site of neural crest producti on. Expression of excess lunatic fringe in the cranial neural tube and neur al crest by retrovirally mediated gene transfer resulted in a significant i ncrease (similar to 60%) in the percentage of cranial neural crest cells 1 day after infection. This effect was mediated by an increase in cell divisi on 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 l umen of the neural tube, confirming that excess fringe modulates Notch sign aling. These findings point to a novel role for lunatic fringe in regulatin g cell division and/or production of neural crest cells by the neural tube. (C) 2001 Academic Press.