Shootin1b Mediates a Mechanical Clutch to Produce Force for Neuronal Migration

Takunori Minegishi,Yasuyuki Uesugi,Naoko Kaneko,Wataru Yoshida,Kazunobu Sawamoto,Naoyuki Inagaki

doi:10.1016/j.celrep.2018.09.068

Takunori Minegishi, Yasuyuki Uesugi + Show 4 more

Open Access

https://doi.org/10.1016/j.celrep.2018.09.068

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Abstract

As an essential step for brain morphogenesis, neurons migrate via mechanical interactions with components of their environment such as neighboring cells and the extracellular matrix. However, the molecular mechanism by which neurons exert forces on their environment during migration remains poorly understood. Here, we show that shootin1b is expressed in migrating mouse olfactory interneurons and accumulates at their leading process growth cone. We demonstrate that shootin1b, by binding to cortactin and L1-CAM, couples F-actin retrograde flow and the adhesive substrate as a clutch molecule. Shootin1b-mediated clutch coupling at the growth cone generates traction force on the substrate, thereby promoting leading process extension and subsequent somal translocation of olfactory interneurons. Furthermore, loss of shootin1 causes abnormal positioning of the interneurons and dysgenesis of the olfactory bulb. Our findings indicate that shootin1b plays a key role in force-driven leading process extension, which propels the migration of olfactory interneurons during olfactory bulb formation.

Highlights

Neuronal migration is an essential process for the proper formation of brain architecture and neuronal networks (Marın and Rubenstein, 2003; Ayala et al, 2007)
We show that shootin1b is expressed at high levels along the migratory route of mouse olfactory interneurons and accumulates at the growth cones of their leading process; this accumulation positively correlates with leading process extension
Loss of Shootin1 Causes Dysgenesis of the Olfactory Bulb and Abnormal Positioning of Olfactory Neurons To study the role of shootin1 in brain development, we analyzed shootin1 KO mice (Baba et al, 2018) and found that they exhibited impaired formation of the olfactory bulb

Summary

Introduction

Neuronal migration is an essential process for the proper formation of brain architecture and neuronal networks (Marın and Rubenstein, 2003; Ayala et al, 2007). The leading process plays a pivotal role in neuronal migration (He et al, 2010; Cooper, 2013); the molecular bases underlying somal translocation have been reported (Marın et al, 2010; Solecki, 2012; Cooper, 2013; Evsyukova et al, 2013; Kaneko et al, 2017). Force generated within the leading process is thought to pull the centrosome forward (Marın et al, 2010). Little is known about the molecular mechanism by which neurons exert forces on their environment to drive cell migration

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