Project description:The goal of this study is to understand how IMP2 contributes to T2D traits by regulating pancreatic beta cell growth and function. Islets from control and Rip2;IMP2 mice were generated by deep sequencing. In additon, we also perfomred IMP2 RIP-Seq to identify IMP2 targets.
Project description:RNA-based regulatory mechanisms play important roles in the development and plasticity of neural circuits and neurologic disease. Developing axons provide a well suited model to study RNA-based regulation, and contain specific subsets of mRNAs that are locally translated and have roles in axon pathfinding. However, the RNA-binding proteins involved in axon pathfinding, and their corresponding mRNA targets, are still largely unknown. Here we find that the RNA-binding protein IMP2 (Igf2bp2) is strikingly enriched in developing axon tracts, including in spinal commissural axons. We used the HITS-CLIP approach to perform a genome-wide identification of RNAs that interact directly with IMP2 in the native context of developing brain. This IMP2 interactome was highly enriched for mRNA targets related to axon guidance. Accordingly, IMP2 knockdown in the developing spinal cord led to strong defects in commissural axon trajectories at the midline intermediate target. These results reveal a highly distinctive axonal enrichment of IMP2, show that it interacts with a network of axon guidance-related mRNAs, and reveal its requirement for normal axon pathfinding during vertebrate development. CLIP-seq
Project description:Data showing the late 2-cell-stage, control embryos (Imp2♀+/♂+) and Imp2-knockout embryos (Imp2♀−/♂+) for HPLC MS/MS analysis. 3 replicates were performed using 330 embryos per group.
Project description:RNA-based regulatory mechanisms play important roles in the development and plasticity of neural circuits and neurologic disease. Developing axons provide a well suited model to study RNA-based regulation, and contain specific subsets of mRNAs that are locally translated and have roles in axon pathfinding. However, the RNA-binding proteins involved in axon pathfinding, and their corresponding mRNA targets, are still largely unknown. Here we find that the RNA-binding protein IMP2 (Igf2bp2) is strikingly enriched in developing axon tracts, including in spinal commissural axons. We used the HITS-CLIP approach to perform a genome-wide identification of RNAs that interact directly with IMP2 in the native context of developing brain. This IMP2 interactome was highly enriched for mRNA targets related to axon guidance. Accordingly, IMP2 knockdown in the developing spinal cord led to strong defects in commissural axon trajectories at the midline intermediate target. These results reveal a highly distinctive axonal enrichment of IMP2, show that it interacts with a network of axon guidance-related mRNAs, and reveal its requirement for normal axon pathfinding during vertebrate development.
Project description:Imp2 -/- mice were subjected to a number of characterization assays, including RNA-Seq of various tissues, Characterization of IMP2 -/- mice including various metabolic measurements.
Project description:Using IMP2-deficient mice to study the role of the RNA-binding protein (RBP) IMP2 in models of autoimmunity, namely autoimmune glomerulonephritis