PT  - JOURNAL ARTICLE
AU  - Kazuma Fujikake
AU  - Masato Sawada
AU  - Takao Hikita
AU  - Yayoi Seto
AU  - Naoko Kaneko
AU  - Vicente Herranz-Pérez
AU  - Natsuki Dohi
AU  - Natsumi Homma
AU  - Satoshi Osaga
AU  - Yuchio Yanagawa
AU  - Toshihiro Akaike
AU  - Jose Manuel García-Verdugo
AU  - Mitsuharu Hattori
AU  - Kazuya Sobue
AU  - Kazunobu Sawamoto
TI  - Detachment of chain-forming neuroblasts by Fyn-mediated control of cell-cell adhesion in the postnatal brain
AID  - 10.1523/JNEUROSCI.1960-17.2018
DP  - 2018 Apr 16
TA  - The Journal of Neuroscience
PG  - 1960-17
4099  - http://www.jneurosci.org/content/early/2018/04/16/JNEUROSCI.1960-17.2018.short
4100  - http://www.jneurosci.org/content/early/2018/04/16/JNEUROSCI.1960-17.2018.full
AB  - In the rodent olfactory system, neuroblasts produced in the ventricular-subventricular zone of the postnatal brain migrate tangentially in chain-like cell aggregates toward the olfactory bulb (OB) through the rostral migratory stream (RMS). After reaching the OB, the chains are dissociated and the neuroblasts migrate individually and radially toward their final destination. The cellular and molecular mechanisms controlling cell-cell adhesion during this detachment remain unclear. Here we report that Fyn, a non-receptor tyrosine kinase, regulates the detachment of neuroblasts from chains in the male and female mouse OB. By performing chemical screening and in vivo loss- and gain-of-function experiments, we found that Fyn promotes somal disengagement from the chains, and is involved in neuronal migration from the RMS into the granule cell layer of the OB. Fyn knockdown or Dab1 deficiency caused p120-catenin to accumulate and adherens junction-like structures to be sustained at the contact sites between neuroblasts. Moreover, a Fyn and N-cadherin double-knockdown experiment indicated that Fyn regulates the N-cadherin-mediated cell adhesion between neuroblasts. These results suggest that the Fyn-mediated control of cell-cell adhesion is critical for the detachment of chain-forming neuroblasts in the postnatal OB.SIGNIFICANCE STATEMENTIn the postnatal brain, newly born neurons (neuroblasts) migrate in chain-like cell aggregates toward their destination, where they are dissociated into individual cells and mature. The cellular and molecular mechanisms controlling the detachment of neuroblasts from chains are not understood. Here we show that Fyn, a non-receptor tyrosine kinase, promotes the somal detachment of neuroblasts from chains, and that this regulation is critical for the efficient migration of neuroblasts to their destination. We further show that Fyn and Dab1 decrease the cell-cell adhesion between chain-forming neuroblasts, which involves adherens junction-like structures. Our results suggest that Fyn-mediated regulation of the cell-cell adhesion of neuroblasts is critical for their detachment from chains in the postnatal brain.