Fig. 9.

A model to explain dumbbell-shaped nuclei and naked chromatin in migrating neurons of Lmnb1^CS/CS mice. (Left) The nuclear lamina (green) in neurons of wild-type mice (Lmnb1^+/+) is tightly woven and is affixed to the inner nuclear membrane by the farnesyl lipid anchors on B-type lamins (red). During neuronal migration, the nucleus is pulled by microtubule-associated dynein motors (yellow) toward the centrosome (orange) in the leading edge of the cell. Pulling the nucleus forward depends on connections between the microtubule network (gray strands) and the LINC complex of the nuclear envelope (SUN1/2, purple; Nesprin-1/2 pink) as well as connections between the LINC complex and the nuclear lamina. (Right) In Lmnb1^CS/CS neurons, the nuclear lamina is no longer tightly affixed to the inner nuclear membrane because of the absence of the farnesyl lipid anchor on lamin B1 (creating a potential space between the nuclear lamina and the inner nuclear membrane). In addition, the B-type lamins exhibit a honeycomb distribution (i.e., the “nuclear lamina meshwork” is not tightly woven). During neuronal migration, the nuclear lamina is pulled forward, exactly as in wild-type mice, but the chromatin (blue) escapes from the confines of the nuclear lamina (through honeycomb-like pores) into the space between the nuclear lamina and inner nuclear membrane. This process creates dumbbell-shaped nuclei in which the nuclear lamina is in one end of the dumbbell (closest to the leading edge of the cell); the bulk of the chromatin is located in the other end of the dumbbell (surrounded by nuclear membranes).