International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

G10 "Telling Time": Lunatic Fringe and Somite Segmentation

Susan E. Cole, John M. Levorse and Thomas F. Vogt. Department of Molecular Biology, Princeton University, Princeton, NJ 09544

The establishment of boundaries within fields of cells is a critical feature of developmental growth and patterning. The Drosophila gene fringe has been shown to play an important role in the establishment of boundaries in the wing and eye by modulating the activity of the Notch pathway. We have previously identified three mammalian homologs of fringe whose expression patterns demarcate developmental boundaries that occur in the limb, hindbrain and somites. Lunatic fringe (Lfng) has been demonstrated to be required to establish developmental boundaries during somitogenesis, a process dependent on Notch signaling. The nature of the patterning mechanism controlling the regulation of somite formation is a fundamental question in developmental biology. Theoretical models have invoked a molecular "clock" that is required to regulate somitogenesis. Recent molecular data has suggested c-hairy and Lfng as candidate genes that may be involved in the clock mechanism. In the presomitic mesoderm (PSM) in the mouse, Lfng RNA expression cycles every 2 hours, the amount of time required to form a pair of somites, implicating Lfng as a component linking Notch signaling to the molecular clock. To help elucidate the clock mechanism we have utilized mouse transgenesis to localize the cis-acting regulatory elements that link Lfng expression to the segmentation clock. We have identified regulatory elements sufficient to direct cyclic Lfng expression in the PSM and somites. In addition, we have identified distinct regulatory elements that are required to direct expression in the hindbrain and ventral neural tube. By generating comparative sequence data for these regions we have identified conserved sequences within the equivalent human LFNG flanking regions that may further demarcate cis acting elements as well as suggesting candidate transcription factors required for regulation of Lfng expression. These defined regulatory elements enable us to direct the expression of Lfng and other fringe family members to examine structure - function relationships, and to further elucidate the mechanism whereby Lfng links Notch signaling to the segmentation clock.

 


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