Building brains: neural chimeras in the study of nervous system development and repair

Abstract

The ability to isolate multipotential neuroepithelial precursor cells from the mammalian nervous system provides exciting perspectives for the in vitro analysis of early nervous system development and the generation of donor cells for neural repair. New models are needed to study the properties of these cells in vivo. Neural chimeras have revealed a remarkable degree of plasticity in the developmental potential of neuroepithelial precursor cells. Following transplantation into the cerebral ventricle of embryonic hosts, precursors derived from various brain regions and developmental stages participate in host brain development and undergo region-specific differentiation into neurons and glia. These findings indicate that in the developing nervous system, migration and differentiation of neural precursors cells are regulated to a large extent by extrinsic signals. Neural chimeras composed of genetically modified cells will permit the study of the molecular mechanisms underlying these guidance cues, which may eventually be exploited for cell replacement strategies in the adult brain. A key problem in neural transplantation is the availability of suitable donor tissue. Neural chimeras composed of embryonic stem (ES) cell-derived neurons and glia depict ES cells as a versatile and virtually unlimited donor source for neural repair. Generation of interspecies neural chimeras composed of human and rodent cells facilitates the translation of these advances into clinical strategies for human nervous system repair.