Actomyosin Contraction at the Cell Rear Drives Nuclear Translocation in Migrating Cortical Interneurons

Abstract

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.

The effect of levetiracetam on midline closure in early chicken embryos

“…Contraction of elements occurring in skeletal structures depends on calcium ion. Thus, calcium (Ca) ion plays a key role in changing skeletal structure and contraction (9).…”

Dynamics of the leading process, nucleus, and Golgi apparatus of migrating cortical interneurons in living mouse embryos

“…Studies using cerebellar granule cells have indicated that the LP myosin II near the nucleus may function to pull the centrosome and the soma (7), whereas another using dissociated granule cells showed evidence that the tip of the LP pulls the soma forward during neuronal migration via a myosin II-dependent forward F-actin flow (11). Other reports have suggested that the activity of the actomyosin system at the rear of the soma generates the forward force (3,4,9,12).…”

“…Studies using real-time imaging of neurons in dissociated culture have demonstrated various aspects of neuronal migration, including the fact that radial fibers (1) and neighboring cells (2) act as the substrate for migration and the molecular mechanisms driving nucleokinesis (3, 4). Real-time imaging has also helped reveal the dynamics and roles of cytoplasmic organelles and cytoskeletal components, such as the centrosome (5-9), microtubules (9), and even of some molecules like calcium (10) and actin (7,11,12) during migration. In addition, slice and explant preparations have demonstrated aspects of migratory behaviors, including locomotion and translocation (13), branch-induced changes in migratory direction (14), multidirectional migration (15), random-walk-like behavior (16), pausing behavior, and the transition from tangential to radial migration (17).…”

Spatiotemporal dynamics of traction forces show three contraction centers in migratory neurons

“…Jian Jiang, 1,2 Zheng-hong Zhang, 1 Xiao-bin Yuan, 1 and Mu-ming Poo force generation that drive soma translocation: the soma may be pulled by the proximal region of the LP (pLPs; Solecki et al, 2009) or the growth cone of the LP (He et al, 2010), or pushed by the TP (Martini and Valdeolmillos, 2010). In addition, there is evidence that microtubules (MTs) may also be involved in regulating neuronal migration, as suggested by the finding that MT depolymerization induced by pharmacological agents or down-regulation of the motor protein kinesin-5 by RNA interference could accelerate neuron migration (He et al, 2010;Falnikar et al, 2011).…”