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Cortical Proteins are Chemokinetic to Cells from the Medial Ganglionic Eminence

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Technical Report

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Uniformed Services University Of The Health Sciences Bethesda United States

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During embryonic development, a majority of neocortical interneurons originate from the medial ganglionic eminence MGE and migrate into the cortex along a path tangential to existing cortical cytoarchitecture. While many cortical proteins are chemoattractant to MGE cells into the cortex, the chemokinetic nature of these factors has not been completely addressed. To better understand the influence of cortical proteins we searched for isoelectric fractions of neocortical extract from E14, E15, and E17 Sprague-Dawley rats that induced migratory activity in MGE cells of isochronic animals. Using multiwell migration assays, we found ganglionic eminence GE cell migration was most significant in the presence of pH 5.5 and 8.5 fractions for E14 and E15 animals, respectively. We also tested the migratory response of MGE cells to defined factors present in the neocortex during this stage of development these included glial-derived neurotrophic factor GDNF, neuregulin NRG, reelin, and glutamate. Significant migration of E15 and E17 MGE cells occurred in the presence of glutamate and NRG. In the multiwell migration assay we observed that E15 MGE cells have a significant chemokinetic reaction to pH 8.5, but not NRG1. Interestingly, imaging of GE explants again demonstrated that the pH 8.5 fraction induced MGE cells to significantly increase the velocity of migration. Therefore, kinesis may be a vital component of MGE cell migration into and within the cortex. These results indicate the likely value of kinetic factors in migration and the distribution of interneurons in the developing neocortex.

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