Fate mapping of the mouse midbrain–hindbrain constriction using a site-specific recombination system

The mouse midbrain–hindbrain constriction is centrally involved in patterning of the midbrain and anterior hindbrain (cerebellum), as revealed by recent genetic studies using mice and embryological studies in chick (reviewed in [1] and [2]). This region can act as an organizer region to induce midbrain and cerebellar development. Genes such as Engrailed-1, Pax-2 and Pax-5, which are expressed in the embryonic cells that will form the midbrain and the cerebellum, are required for development of these regions. Fate-mapping experiments at early somite stages in chick have revealed that the cerebellar primordium is located both anterior and posterior to the midbrain–hindbrain constriction, whereas midbrain precursors lie more anteriorly. Fate mapping in mice has been complicated by the inaccessibility of the postimplantation embryo. Here, we report the use of a new in vivo approach involving the Cre–loxP site-specific recombination system [3] to map the fate of cells in the mouse midbrain–hindbrain constriction. We show that cells originating in the mouse dorsal midbrain–hindbrain constriction during embryonic days 9–12 contribute significantly to the medial cerebellum and colliculi. Our data demonstrate the feasibility of using a recombinase-based lineage-tracing system for fate mapping in the mouse