【Research News】PlexinD1 signaling controls morphological changes and migration termination in newborn neurons
Much recent research has focused on the molecular mechanisms that control neuronal migration. While newly born neurons maintain a very simple, immature morphology and migrate in a saltatory manner toward their final destination, during the termination of migration, they undergo prominent morphological changes, which lead to the development of dendrites and functional neuronal circuitry. However, the mechanisms by which the morphological changes induce the termination of neuronal migration have not been demonstrated.
In this study, the authors report a mechanism by which the termination of new-neuron migration is maintained in the postnatal olfactory bulb (OB) (Fig. 1). Upon approaching their destination, new neurons transiently extended a protrusion from the proximal region of their leading process during the resting phase of migration, which they refer to as a filopodia-like lateral protrusion (FLP). The FLP formation is induced by PlexinD1 downregulation and local Rac1 activation, which coincide with microtubule reorganization and the pausing of somal translocation. By using a photoswitchable inhibitor of microtubule polymerization, they revealed that the somal translocation of resting neurons is suppressed by microtubule polymerization within the FLP. The timing of new-neuron migration termination, controlled by Sema3E-PlexinD1-Rac1 signaling, influences the neurons' final positioning, dendritic patterns, and functions in the postnatal OB. Their results suggest that the PlexinD1 signaling controls FLP formation and neuronal migration termination through the precise control of microtubule dynamics.
The regulatory mechanism involving FLP formation enables the precise control of neuronal migration termination in brain development, and may be involved in neurological disorders caused by impaired neuronal migration. After brain injury, newborn neurons migrate toward the lesion and differentiate into mature neurons, which contribute to neuronal regeneration and functional recovery. Therefore, PlexinD1 signaling-mediated control of FLP formation and neuronal migration termination in newborn neurons may provide novel therapeutics for neuronal tissue regeneration.
Fig. 1. Summary of this study.
The regulatory mechanism involving FLP formation links neuronal migration termination and the initiation of differentiation, contributing to the positioning and functions of newborn neurons in the postnatal OB.
Published Online Date :18 January, 2018
Journal:The EMBO Journal
|Title||PlexinD1 signaling controls morphological changes and migration termination in newborn neurons|
|Author||Masato Sawada, Nobuhiko Ohno, Mitsuyasu Kawaguchi, Shih-hui Huang, Takao Hikita, Youmei Sakurai, Huy Bang Nguyen, Truc Quynh Thai, Yuri Ishido, Yutaka Yoshida, Hidehiko Nakagawa, Akiyoshi Uemura, and Kazunobu Sawamoto