hairy-related genes (chick hairy1 and chick hairy2, avian homologues of mouse Hes1), of lunatic fringe (Lfng) in chick presomitic mesoderm, and of Hes1 and Lfng in mouse

In vertebrates, somite formation precedes the segmental appearance of the vertebral column, trunk musculature and peripheral nerves. The somites are generated by segmentation of the paraxial mesoderm on either side of the neural tube and notochord, where they form as pseudoepithelial spheres. Newly formed somites are a mosaic of presumptive rostral and caudal cells. A number of differences exist between the rostral and caudal sclerotome halves, reflected, that is, by the specific expression of several marker genes (Stern and Keynes, 1987; Yamaguchi et al., 1992; Candia et al., 1992; Bettenhausen et al., 1995; Rovescalli et al., 1996; Mansouri et al., 1997; Saga et al., 1997). The rostrocaudal polarity of each somite is already established within the presomitic mesoderm. The specification of the rostral and caudal compartments is plays an important role in the formation of segment boundaries (Aoyama and Asamoto, 1988; Swiatek et al., 1994; Conlon et al., 1995; Hrabe de Angelis et al., 1997; Saga et al., 1997). Insight into the segmentation of the somites has recently been obtained from observations of the rhythmic expression of hairy-related genes (chick hairy1 and chick hairy2, avian homologues of mouse Hes1), of lunatic fringe (Lfng) in chick presomitic mesoderm, and of Hes1 and Lfng in mouse presomitic mesoderm (Palmeirim et al., 1997; McGrew et al., 1998; Aulehla and Johnson, 1999; Jouve et al., 2000). Since the Lfng gene product is essential for normal segmentation of somites, a molecular clock represented by the cyclic expression of Lfng seems to be involved in somite segmentation (Zhang et al., 1998; Evrard et al., 1998). The Lfng gene product apparently functions via the Notch signalling pathway during segmentation of the somitic mesoderm for the following reasons: First, fringe products are required for the Deltadependent proteolytic activation of Notch by presenilins in both invertebrates and vertebrates (Panin et al., 1997; Cohen et al., 1997; Irvine 1999; Moloney et al., 2000; Brückner et al., 2000; Hicks et al., 2000). Second, segmentation of the somitic mesoderm is affected in Notch1, Delta-like1 (Dll1), Dll3 and presenilin 1 (Ps1; encoded by Psen1 – Mouse Genome Informatics) -deficient mice (Swiatek et al., 1994; Conlon et al., 1995; Hrabe de Angelis et al., 1997; Wong et al., 1997; Shen et al., 1997; Kusumi et al., 1998). Therefore, the Notch 1391 Development 128, 1391-1402 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV2688