Development and migration of GABAergic neurons in the mouse myelencephalon

Abstract

GABAergic neurons are the major inhibitory interneurons that are widely distributed in the central nervous system. It is well established that they originate from a focal region in the embryonic forebrain during development, and then migrate to other regions such as the neocortex. However, the migration of GABAergic neurons remains obscure in other axial levels of the brain. We examined the early development of myelencephalic GABAergic neurons using glutamate decarboxylase 67 / green fluorescent protein (GAD67-GFP) knocking mice. Observation of fixed tissues in coronal sections and flat whole-mount preparations indicated that, while GFP-positive cells are restricted to the subpial region in the ventral aspect of the myelencephalon at an early stage, they spread dorsally and eventually occupy the entire region of the myelencephalon as development proceeds. We developed a flat-mount in vitro preparation in which these patterns of development could be recapitulated. Transplantation of dorsal myelencephalic tissue of a wildtype embryo to a corresponding region of GAD67-GFP mouse embryos clearly demonstrated invasion of dorsally oriented GABAergic neurons from host to donor tissue. These results indicate that ventral-to-dorsal tangential migration of GABAergic neurons takes place in the myelencephalon. Our results extend the observations in the forebrain that inhibitory and excitatory neurons in a specific brain compartment take distinct migratory paths.