Nuclear movement is critical for several developmental processes in eukaryo
tes. Drosophila oogenesis provides a paradigmatic example in which localiza
tion of the nucleus generates a source of cellular asymmetry that is used i
n patterning both the anterior-posterior and the dorsal-ventral axes of the
oocyte. In this study we show that mutations in the Drosophila Lissencepha
ly1 (DLis1) gene result in partial ventralization of the eggshell. DLis1 mu
tations affect the localization of gurken mRNA and protein in the oocyte. T
hese defects are correlated with incorrect positioning of the oocyte nucleu
s, suggesting that DLis1 is required for nuclear migration. DLis1 shows sig
nificant sequence conservation across the evolutionary spectrum. Fungal cog
nates of DLis1 are involved in nuclear migration while homologs in humans a
nd mice are implicated in neuronal migration. DLis1 shows genetic interacti
ons with the Glued and Dynein heavy chain subunits of the dynein/dynactin c
omplex, supporting the idea that the Lis1 family of proteins plays a role i
n microtubule motor-based nuclear motility. (C) 2000 Academic Press.