Examining the role of Deltalike3 in Notch Signaling during Vertebrate Segmentation
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Date
2008-06
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The Ohio State University
Abstract
Somitogenesis is an embryological process regulated by the Notch signaling pathway. Somites are the precursors to the vertebrae and ribs and they bud from the pre-somitic mesoderm (PSM). This process is regulated by a clock that times the process and by mechanisms that regulate somite patterning. Mutations in the Notch pathway perturb both the clock and patterning activities during somitogenesis and disrupt normal skeletal development. Lunatic fringe (Lfng), a Notch family member, plays separable roles in the clock and patterning mechanisms during somitogenesis. Loss of Lfng in mice results in malformed vertebrae, truncated tails, and fused ribs. This phenotype is also seen in mice lacking Deltalike3 (Dll3), an unusual Notch ligand. Furthermore, mutations in either Dll3 or Lfng can be responsible for the disease spondylocostal dysostosis in humans, which is characterized by disorganized ribs and vertebrae. These similarities suggest that Dll3 and Lfng may have overlapping roles during somitogenesis. However, many open questions remain about Dll3’s role during somitogenesis and Notch signaling: (1) Is Dll3 an inhibitor or activator of Notch? (2) Does Dll3 play important roles in the clock or patterning activities of Notch signaling or both? (3) Do Lfng and Dll3 act together or separately during Notch signaling? To determine if Dll3 is an activator or inhibitor of Notch, we are examining the activation of the Notch receptor and the expression of Notch target genes in Dll3 null (Dll3pu/pu) embryos. To dissect the roles played by Dll3 in the clock and in somite patterning, a transgene was designed to specifically drive Dll3 expression in the patterning of somites but not within the clock. Experiments are underway to assay the expression of the transgenes in the PSM of embryos. Finally, to examine the potential functional overlaps between Lfng and Dll3, double heterozygous mice for Dll3 and Lfng (Dll3 +/pu; Lfng +/-) and homozygous null mice for Dll3 and Lfng (Dll3 pu/pu; Lfng -/-) are being examined for unique skeletal phenotypes. The results from these studies suggest that Dll3 and Lfng do not have overlapping roles during Notch signaling.
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(1st place) 2008 OSU Richard J. and Martha D. Denman Undergraduate Research forum
(Winner) 2008 OSU College of Biological Sciences Undergraduate Research Colloquium
(Winner) 2008 OSU College of Biological Sciences Undergraduate Research Colloquium
Keywords
Dll3, Lfng, Notch, somitogenesis