The lunatic Fringe gene is a target of the molecular clock linked to somite segmentation in avian embryos

AbstractThe most obvious segments of the vertebrate embryo are the trunk mesodermal somites which give rise to the segmented vertebral column and the skeletal muscles of the body. Mechanistic insights into vertebrate somitogenesis have recently been gained from observations of rhythmic expression of the avian hairy-related gene (c-hairy1) in chick presomitic mesoderm (PSM), suggesting the existence of a molecular clock linked to somite segmentation ([1]; reviewed in [2]). Here, we show that lunatic Fringe (lFng), a vertebrate homolog of the Drosophila Fringe gene, is also expressed rhythmically in PSM. The PSM expression of lFng was observed as coordinated pulses of mRNA resembling the expression of c-hairy1. We show that c-hairy1 and lFng expression in the PSM are coincident, indicating that both genes are responding to the same segmentation clock. The genes were found to differ in their regulation, however; in contrast to c-hairy1, lFng mRNA oscillations required continued protein synthesis, suggesting that lFng could be acting downstream of c-hairy1 in the clock mechanism. In Drosophila, Fringe has been shown to play a role in modulating Notch–Delta signalling [3,4], a pathway which in vertebrates has been implicated in defining somite boundaries [5–9]. These observations place the segmentation clock upstream of the Notch–Delta pathway during vertebrate somitogenesis