The overall goal of this proposal is to develop a means of visualizing cells injected into the early mouse brain embryo and other tissues with high resoution MR micro-imaging, in vivo, in order to study the integration and proliferation patterns of the transplanted neural progenitors. The applicants propose to make use of a 16 amino-acid peptide, the third helix of the Drosophila Antennapedia homeodomain, which has recently been shown to b capable of translocating through cell membranes with large molecular weight molecules attached to the peptide.
The specific aims of the proposed research are the following. 1) Synthesize novel peptide conjugates with gadolinium-base MR contrast agents and the 16 peptide homeodomain. 2) Evaluate the peptide-Gd conjugate for its potential to be internalized by cultured neural cell lines and primary neural cells, and quantitate the resulting MR contrast enhancement of cells in vitro. 3) Evaluate the utility of these MR-labeled cells for studying in vivo integration and proliferation patterns of neural progenitors. MR-labeled cells will be injected into specific target regions in the brains o mouse embryos staged between gestational ages 9.5 to 13.5 days, and 3D MR imag data will be collected and analyzed from individual embryos at selected timepoints up to 72 hours after injection.
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