Abstract

The embryonic development of the cortex involves a phase of long distance migration of interneurons born in the basal telencephalon. Interneurons first migrate tangentially and then reorient their trajectories radially to enter the developing cortex. We have shown that migrating interneurons can assemble a primary cilium, which maintains the centrosome to the plasma membrane and processes signals to control interneuron trajectory (Baudoin et al., 2012). In the developing cortex, N-cadherin is expressed by migrating interneurons and by cells in their migratory pathway. N-cadherin promotes the motility and maintains the polarity of tangentially migrating interneurons (Luccardini et al., 2013). Because N-cadherin is an important factor that regulates the migration of medial ganglionic eminence (MGE) cells in vivo, we further characterized the motility and polarity of MGE cells on a substrate that only comprises this protein. MGE cells migrating on a N-cadherin substrate were seven times faster than on a laminin substrate and two times faster than on a substrate of cortical cells. A primary cilium was much less frequently observed on MGE cells migrating on N-cadherin than on laminin. Nevertheless, the mature centriole (MC) frequently docked to the plasma membrane in MGE cells migrating on N-cadherin, suggesting that plasma membrane docking is a basic feature of the centrosome in migrating MGE cells. On the N-cadherin substrate, centrosomal and nuclear movements were remarkably synchronous and the centrosome remained near the nucleus. Interestingly, MGE cells with cadherin invalidation presented centrosomal movements no longer coordinated with nuclear movements. In summary, MGE cells migrating on a pure substrate of N-cadherin show fast, coordinated nuclear and centrosomal movements, and rarely present a primary cilium.

Highlights

  • Cell migration, including neuronal migration, is described as a repetitive process comprising several steps (Ridley et al, 2003; Valiente and Marín, 2010): (i) cell polarization; (ii) leading process elongation; (iii) leading process stabilization through the formation of adherent junctions and/or adhesive contacts; (iv) forward displacement of organelles by forces anchored on adhesion sites; and (v) tail retraction

  • We have recently shown that the mature centriole (MC) of medial ganglionic eminence (MGE) cells can dock to the plasma membrane and organize a short primary cilium at the cell surface (Baudoin et al, 2012)

  • The longest nuclear-centrosomal distances were observed in MGE cells cultured on cortical axons rather than in MGE cells cultured on N-cadFc (Table in Figure 3G, mean value 7.6 μm, significantly different by a t-test, p = 0.0053). These results show that the centrosome of MGE cells migrating on pure N-cadherin distributed in a perinuclear domain significantly larger than in MGE cells cultured on cortical axons

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Summary

Introduction

Cell migration, including neuronal migration, is described as a repetitive process comprising several steps (Ridley et al, 2003; Valiente and Marín, 2010): (i) cell polarization; (ii) leading process elongation; (iii) leading process stabilization through the formation of adherent junctions and/or adhesive contacts; (iv) forward displacement of organelles by forces anchored on adhesion sites; and (v) tail retraction. Recent studies have demonstrated a major role of N-cadherin mediated cell-cell adhesion in the radial migration of principal cortical neurons in the mouse embryo (Kawauchi et al, 2010; Franco et al, 2011; Jossin and Cooper, 2011). They showed that N-cadherin recycling controls the adhesion of migrating neurons to the radial glia, and that N-cadherinmediated adhesion functionally interacts with the reelin signaling pathway to control transition steps at the beginning and at the end of the radial migration. Whether centrosome positioning organizes cell polarity or stabilizes a polarized organization resulting from interactions with extrinsic cues, is unclear in migrating cells of which the centrosome is most often positioned in front of the nucleus (Ueda et al, 1997; Solecki et al, 2004; Higginbotham and Gleeson, 2007; Yanagida et al, 2012)

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