The Hatten Lab Projects


The GENSAT Project - Novel CNS Migration Pathways



The Gensat Project carried out together with the Heintz Lab, and with members of the GENSAT Project, has allowed us to screen the expression patterns of a large number of CNS genes to probe for genes that might function in neuronal migration. We are using a number of the BAC transgenic lines to study both granule cell migration in cerebellum and the migration of cells in layer 1 of the neocortex. For the cerebellar cortex, we are analyzing HGF and receptor c-Met during glial-guided migration. In the neocortex, we are examining novel pathways of the migration of layer 1 neurons. Contrary to the traditional view where layer1 neurons migrate out through the wall of the cortex, the Pdel1c BAC transgenic line, as well as three other lines, demonstrate that these neurons arise in the anterior aspect of the developing neocortex and migrate across the surface of the structure as development proceeds (Gong et al, 2003, Nature). In this regard, the migration pathway resembles that of the EGL cells in the cerebellum. We are therefore imaging the migration of these cells as well as using genetic methods to dissect the mechanisms of their migration.

Expression of Phosphodiesterase 1C reveals a novel and distinct migratory pathway in developing brain. At embryonic day 10.5 (E10.5), EGFP+ cells along the dorsal aspect of the neural tube. At embryonic day 15.5 (e15.5) labelled cells in the anterior portion and superficial aspect of the cortex. At higher magnification, right e15.5, cells above the cortical plate are labelled. At P7, cells in layer 1 of the cortex are labelled (large arrows). Right panel, higher magnification and Confocal microscopy (inset) - layer 1 Cajal Retzius cells express the reporter gene. Cells that undergo a similar pattern of migration, the cerebellar granule cells, are also labelled, as are cells in the olfactory bulb and pontine nucleus. (Reprinted from Gong et al, 2003).

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