Cellular and molecular dynamics of neuronal migration

Neurons are generated from neural stem cells in the germinal layer, and then migrate through the crowded neural tissues toward their specific sites of function within the cortex. Failure in neuronal migration may cause severe brain malformation and psychiatric disorders.




Cerebellar granule cells are the excitatory interneurons of the cerebellar cortex, which undergo significant migration during cortex formation. We have established a time-lapse imaging system for quantitative analyses of granule cell migration in organotypic cultures, which retain the cell architecture and environment of the cerebellar cortex. We have successfully visualized organelle dynamics in migrating neurons in the brain tissue and have proposed a novel model for neuronal migration (Umeshima et al., 2007, Umeshima and Kengaku, 2013).

We have recently developed an in vitro system for analyses of motion dynamics of neuronal migration at a high spatio-temporal resolution using spinning-disc confocal microscopy. We have found that the migrating nucleus exhibits highly dynamic motion, including sharp deformation and rotation, suggesting the involvement of mutiple motor systems (Wu et al., 2018). We now seek to visualize the force which drives migration, by quantitative measurement of the rheological properties of migrating neurons. Cerebellar granule cells are the excitatory interneurons of the cerebellar cortex, which undergo significant migration during cortex formation.

小脳皮質の介在ニューロンである顆粒細胞は、発生過程で最も大規模に移動する細胞のひとつです。我々は生後発達中の小脳組織を器官培養し、皮質内を移動する顆粒細胞の動きを長時間観察するリアルタイムイメージング系を確立しています。このシステムを用い、組織内を移動するニューロンのオルガネラのダイナミクスの観察に世界に先駆けて成功しました(Umeshima et al., 2007, Umeshima and Kengaku, 2013)。スピニングディスク型共焦点顕微鏡を用いてさらに時空間解像度を上げて観察すると、ニューロン核は前進のみでなく回転や変形など、複数のモーター分子活性を示唆する複雑な動きを伴うことが明らかになりました(Wu et al., 2018)。


Migratory granule cells in cultured cerebellar tissue



Nuclear dynamics of migratory granule cells


培養下で移動する顆粒細胞の核(H2B:マゼンダ、白)と微小管(Dcx; 緑)を高時空間解像タイムラプスにより観察した。


Wu, Y.K., Umeshima, H., Kurisu, J. and Kengaku, M. (2018) Nesprins and opposing microtubule motors generate a point force driving directional nuclear motion in migrating neurons. Development. 2018 Mar 8; 145(5) pii: dev158782.

Nakashima, K., Umeshima, H. and Kengaku M. (2015) Cerebellar granule cells are predominantly generated by terminal symmetric divisions of granule cell precursors. Dev. Dyn. 244(6):748-758

Umeshima, H. and Kengaku, M. (2013) Differential roles of cyclin-dependent kinase 5 in tangential and radial migration of cerebellar granule cells. Mol Cell Neurosci. 52:62-72.

Umeshima, H., Hirano T and Kengaku M. (2007) Microtubule-based nuclear movement occurs independently of centrosome positioning in migrating neurons. Proc. Natl. Acad. Sci. U S A 104:16182-16187.