Midbrain and cerebellum development depends on an organizing center that is located at the midbrainhindbrain junction of the vertebrate embryo. Expression of the two closely related transcription factors Pax2 and Pax5 overlaps spatially and temporally in this region of the developing central nervous system. To study a possible interaction of these transcription factors in midbrain and cerebellum patterning, we have generated Pax5, Krd double mutant mice. The transgene-induced Krd mutation corresponds to an Ϸ7-centimorgan chromosome 19 deletion that eliminates the entire Pax2 locus. The heterozygous Krd mutation deleting one Pax2 allele had no effect on midbrain and cerebellum development. Moreover, only minor developmental defects were previously observed at the midline of the inferior colliculus and anterior cerebellum in mice that were homozygous for a targeted Pax5 mutation. Similar morphological alterations were observed in 80% of all compound heterozygous Pax5 (؉͞؊) Krd (؉͞؊) mice. However, in the remaining 20% of compound heterozygotes, the inferior colliculi were missing, and the vermis of the cerebellum was severely disrupted due to the failure of the cerebellar primordia to fuse at the midline. Inactivation of the second Pax5 allele in Pax5 (؊͞؊) Krd (؉͞؊) mice resulted in complete loss of the posterior midbrain and cerebellum, as the tissue originating from the midbrain-hindbrain boundary region was deleted in the embryo as early as day 9.5. On the basis of these data, we propose that the cooperation of Pax2 and Pax5 is essential for normal functioning of the organizing center at the midbrainhindbrain junction.

A conserved patch of amino acids in the globular tail of type V myosin binds She3p to localize ASH1 mRNA to the bud of dividing yeast cells.

During gastrulation in Xenopus convergence and extension movements, mediated by mediolateral intercalations, are the driving force for early neural plate morphogenesis. Here we show that the winged helix transcriptional regulator, Xfd-12' is dynamically expressed in medial neural plate precursors that undergo convergence and extension movements. These medial neuraxial progenitors are specified in and beyond the Spemann organizer prior to specification of the basal anlage of the neural plate. The initiation of Xfd-12' expression coincides with the induction of mesendoderm by Nodal-related growth factors at the late blastula stage. Comparative expression analysis suggests that cellular rearrangements at the pre-gastrulation stage account for regionalization of the Spemann organizer into head and trunk organizer compartments, the latter in which medial neural plate progenitors reside. While the maintenance of Xfd-12' expression in the dorsal non-involuting marginal zone requires FGF signalling, its subsequent positioning along the medial aspect of the neuraxis depends on signalling by Wnt and Nodal-related family members. Based on these findings we propose that XFD-12' is a trunk organizer component that might control convergence and extension movements of medial neural plate precursors during gastrulation.