Abstract

Neuronal migration is necessary in the process of the formation of brain architecture. Recently, we demonstrated that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons exhibit directional migration in vitro. However, it remains unclear how the cell shape is involved in their migration. In this study, we performed live imaging analyses using human iPSC-derived dopaminergic neurons. Our automated method, which can automatically identify the cell body shape and the cell position at specific time points, revealed that healthy iPSC-derived dopaminergic neurons migrate according to their shape. This migration behavior was out of accord in neurons derived from iPSCs carrying an RELN deletion. Our findings provide a novel theory that cell body orientation is related to the stability of movement direction for human dopaminergic neurons, under the regulation of RELN.

Highlights

  • Neuronal migration is necessary in the process of the formation of brain architecture

  • Our single-cell trajectory analysis using time-lapse images of migrating neurons revealed that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons exhibit directional migration, which was weakened in dopaminergic neurons carrying a rare RELN variant (RELN-del)[5]

  • Cell shape differs in RELN-del dopaminergic neurons

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Summary

Introduction

Neuronal migration is necessary in the process of the formation of brain architecture. We demonstrated that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons exhibit directional migration in vitro It remains unclear how the cell shape is involved in their migration. Our automated method, which can automatically identify the cell body shape and the cell position at specific time points, revealed that healthy iPSC-derived dopaminergic neurons migrate according to their shape. This migration behavior was out of accord in neurons derived from iPSCs carrying an RELN deletion. The present study observed and analyzed the migration behavior of human iPSC-derived dopaminergic neurons using an automated detection system, which can identify the cell body shape and the cell position at specific time points. Migration stability is associated with the robustness of the cell axis rotation, and RELN plays an important role in this process

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