Girdin is an intrinsic regulator of neuroblast chain migration in the rostral migratory stream of the postnatal brain

Naoko Kaneko, Yun Wang, Naoya Asai, Atsushi Enomoto, Mayu Isotani-Sakakibara, Takuya Kato, Masato Asai, Yoshiki Murakumo, Haruko Ota, Takao Hikita, Takashi Namborgnamea, Keisuke Kurodaorgname, Kozo Kaibuchiorgname, Guo Li Mingorgname, Hongjun Songorgname, Kazunobu Sawamotoorgname, Masahide Takahashi

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Abstract

In postnatally developing and adult brains, interneurons of the olfactory bulb (OB) are continuously generated at the subventricular zone of the forebrain. The newborn neuroblasts migrate tangentially to the OB through a well defined pathway, the rostral migratory stream (RMS), where the neuroblasts undergo collective migration termed "chain migration." The cell-intrinsic regulatory mechanism of neuroblast chain migration, however, has not been uncovered. Here we show that mice lacking the actin-binding Akt substrate Girdin (a protein that interacts with Disrupted-In-Schizophrenia 1 to regulate neurogenesis in the dentate gyrus) have profound defects in neuroblast chain migration along theRMS.Analysis of two gene knock-in mice harboring Girdin mutants identified unique amino acid residues in Girdin's C-terminal domain that are responsible for the regulation of neuroblast chain migration but revealed no apparent requirement of Girdin phosphorylation by Akt. Electron microscopic analyses demonstrated the involvement of Girdin in neuroblast cell-cell interactions. These findings suggest that Girdin is an important intrinsic factor that specifically governs neuroblast chain migration along the RMS.

Original languageEnglish
Pages (from-to)8109-8122
Number of pages14
JournalJournal of Neuroscience
Volume31
Issue number22
DOIs
Publication statusPublished - 01-06-2011

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Kaneko, N., Wang, Y., Asai, N., Enomoto, A., Isotani-Sakakibara, M., Kato, T., Asai, M., Murakumo, Y., Ota, H., Hikita, T., Namborgnamea, T., Kurodaorgname, K., Kaibuchiorgname, K., Mingorgname, G. L., Songorgname, H., Sawamotoorgname, K., & Takahashi, M. (2011). Girdin is an intrinsic regulator of neuroblast chain migration in the rostral migratory stream of the postnatal brain. Journal of Neuroscience, 31(22), 8109-8122. https://doi.org/10.1523/JNEUROSCI.1130-11.2011