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Jessica Sweatt
graduate student
Last active: 6/11/2012

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Vertebrates exhibit conserved left-right (LR) internal asymmetries.  The molecular mechanisms initiating asymmetry and the translation into asymmetric morphogenetic processes are poorly understood.  We study the conserved L-side signaling of Nodal (Xnr1/Nodal1 in Xenopus) and its antagonist Lefty (Xlefty) in the left lateral plate mesoderm (L LPM).  Expression of Xnr1 and Xlefty restricted to the L LPM is required for proper organ chirality.  Although the asymmetric Xnr1/Xlefty expression patterns are well described, little is known about how the proteins themselves behave.  Nodal and Lefty are related to TGFβ, being generated as preproproteins, proteolytically cleaved, secreted, and subject to post-translational modifications (e.g. glycosylation).  Many, but not all, TGFβ members contain an N-glycosylation site in the mature protein.  We are determining how the frog Xnr1/Xlefty and mouse Nodal ligands, which are glycosylated or non-glycosylated, respectively, behave at tailbud versus gastrula tissues, focusing on their extracellular stability, intercellular movement, and especially interaction with ECM.   Knowledge of the molecular behaviors and interactions of these ligands will provide fundamental insights into how morphogen signaling is regulated to influence cells and tissues to twist, fold, or undergo asymmetric regression/maintenance, in order to establish correct internal anatomy.

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2213 Garland Ave.
9415 MRB IV
Nashville, TN 37232
USA
615-343-8258 (p)
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Keywords

Left-Right Asymmetry morphogen Nodal TGF&beta Xenopus laevis Xnr1