Date of Award
Doctor of Philosophy (PhD)
Cell migration is the principal determinant of the final brain cytoarchitecture. However, we have only limited knowledge about the migratory pathways and mechanisms utilized during brain development. In m y thesis I present new and unexpected findings about neuronal migration in the developing forebrain. I analyzed and characterized a novel type of neuronal migration, so called tangential chain migration that was first identified in the subventricular zone (SVZ) in the adult mouse brain. I developed an in vitro migration assay using Matrigel as a substrate, which allowed me to analyze dynamics and mechanism of S V Z cell translocation. I demonstrated that neurons migrating in chains move rapidly along each other in the absence of glia, implying that chain migration is different from previously described radial migration. Using the in vitro assay I discovered two regions in the embryonic mouse ventral forebrain containing large numbers of tangentially migrating neurons. I studied migratory potential of these embryonic cells after transplantation into the adult brain. I showed that cells from the medial ganglionic eminence (MGE) demonstrate a novel migratory behavior. M G E cells disperse through the adult brain tissue and differentiate into GABAergic neurons. I showed that M G E cells could disperse even in experimentally lesioned adult brain. Thus, the unique migratory behavior of M G E cells might open new clinical approaches to the repair of damaged brain. Finally, I show that widespread migration of M G E cells reflects their normal behavior in the developing brain. I analyzed migratory potential of M G E cells in vitro and by ultrasound guided transplantation in vivo. These experiments revealed large-scale directional migration of M G E cells into the developing neocortex in embryonic mouse brain. I propose that a ventro-dorsal permissive gradient detected in the developing forebrain might be the principal mechanism guiding M G E cell migration dorsally. In summary, I revealed a population of embryonic neuronal precursors with unprecedented capacity to migrate long distances both in the developing and adult mammalian brain.
Wichterle, Hynek, "The Brain Invaders: Widespread Neuronal Dispersion in Developing and Adult Mammalian Brain" (2000). Student Theses and Dissertations. 332.