A method for rapid gain-of-function studies in the mouse embryonic nervoussystem

We used ultrasound image-guided injections of high-titer retroviral vectors to obtain widespread introduction of genes into the mouse nervous system i n utero as early as embryonic day 8.5 (E8.5). The vectors used included int ernal promoters that substantially improved proviral gene expression in the ventricular zone of the brain. To demonstrate the utility of this system, we extended our previous work in vitro by infecting the telencephalon in vi vo as early as E8.5 with a virus expressing Sonic Hedgehog. Infected embryo s showed gross morphological brain defects, as well as ectopic expression o f ventral telencephalic markers characteristic of either the medial or late ral ganglionic eminences.