Examining the effects of Lunatic fringe dosage in somitogenesis
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Date
2008-06
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The Ohio State University
Abstract
The repeating structures of the vertebrate axial skeleton are produced by the process of somitogenesis. Somites bud from the presomitic mesoderm (PSM) in an anterior to posterior direction, and are the embryonic precursors of the vertebrae and ribs. This process is highly regulated by one signaling pathway in particular: Notch signaling. This study focuses on the functions of Lunatic fringe (Lfng) which encodes a glycosyltransferase that inhibits Notch signaling. The PSM is divided into two regions: one in the posterior region (region I), a clock that times somitogenesis. In the anterior PSM (region II), rostral-caudal (R/C) patterning of somites occurs. Lfng and Notch signaling play roles in both regions of the PSM. Our lab created a novel Lfng allele that perturbs Lfng function in the clock, but preserves its function in R/C somite patterning, and found that while cyclic Lfng actually is important in anterior skeletal development, the Lfng patterning function is specifically required for tail development. This project focuses on the roles played by Lfng and somite patterning in tail development. We examined skeletal development in embryos expressing different amounts of Lfng during R/C patterning. In the absence of anterior Lfng tail development is severely affected and tail truncation is observed. As the expression of Lfng in the anterior PSM increases, less severe tail phenotypes are observed. Data obtained from this experiment suggests that anterior expression of Lfng in the rostral-caudal patterning region is critical for development of the tail and that tail development is sensitive to Lfng dosage. In order to test this hypothesis, a novel transgene expressing exogenous Lfng only in the anterior PSM has been created. We hypothesize that this anterior-specific Lfng will rescue tail development in Lfng null mice. We are currently investigating the effects of this transgene by first analyzing Lfng expression by whole mount in situ hybridization. Currently, mice are being bred in order to provide us with data to support our hypothesis.
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Keywords
Lfng, somitogenesis, segmentation, Notch, FCE, patterning