Actomyosin contraction at the cell rear drives nuclear translocation in migrating cortical interneurons.
Neuronal migration is a complex process requiring the coordinated interaction of cytoskeletal components and regulated by calcium signaling among other factors. Migratory neurons are polarized cells in which the largest intracellular organelle, the nucleus, has to move repeatedly. Current views support a central role for pulling forces that drive nuclear movement. The participation of actomyosin driven forces acting at the nucleus rear has been suggested, however its precise contribution has not been directly addressed. By analyzing interneurons migrating in cortical slices of mouse brains, we have found that nucleokinesis is associated with a precise pattern of actin dynamics characterized by the initial formation of a cup-like actin structure at the rear nuclear pole. Time-lapse experiments show that progressive actomyosin contraction drives the nucleus forward. Nucleokinesis concludes with the complete contraction of the cup-like structure, resulting in an actin spot at the base of the retracting trailing process. Our results demonstrate that this actin remodeling requires a threshold calcium level provided by low-frequency spontaneous fast intracellular calcium transients. Microtubule stabilization with taxol treatment prevents actin remodeling and nucleokinesis, whereas cells with a collapsed microtubule cytoskeleton induced by nocodazole treatment, display nearly normal actin dynamics and nucleokinesis. In summary, the results presented here demonstrate that actomyosin forces acting at the rear side of the nucleus drives nucleokinesis in tangentially migrating interneurons in a process that requires calcium and a dynamic cytoskeleton of microtubules.
Martini
Francisco J
FJ
Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones, Científicas y Universidad Miguel Hernández, 03550 Sant Joan d'Alacant, Spain.
Valdeolmillos
Miguel
M
D000205:Actomyosin / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D007091:Image Processing, Computer-Assisted; D007395:Interneurons / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018715:Microscopy, Video
D000205:Actomyosin