1: Reelin transiently promotes N-cadherin-dependent neuronal adhesion during mouse cortical development.
Science of the Month - April 2017
Proc Natl Acad Sci U S A.
2017 Feb 21;114(8):2048-2053. doi: 10.1073/pnas.1615215114.
Yuki Matsunaga, Mariko Noda, Hideki Murakawa, Kanehiro Hayashi, Arata Nagasaka, Seika Inoue,Takaki Miyata, Takashi Miura, Ken-ichiro Kubo, and Kazunori Nakajima
Cerebral cortical neurons are born near the ventricular surface and migrate toward the brain surface to form a six-layered structure. A secreted protein called Reelin is essential for the proper formation of this structure, and a deficiency in Reelin causes significant disruption of the layered structure. However, how Reelin acts on neurons to control layer formation is not yet well understood.
In this study, we discovered that Reelin promotes N-cadherin-dependent adhesion between neurons, causing them to aggregate. After creating and examining a mathematical model of this aggregation pattern, we predicted that the enhancement of cell adhesion by Reelin is transient rather than sustained. We then investigated this in living cells using an atomic force microscope and confirmed that the enhancement of adhesive force indeed occurs only transiently. Furthermore, when we created conditions in the developing fetal mouse brain where the once-strengthened cell adhesion remained strong and did not weaken, we found that the layered structure was disrupted. From these findings, we concluded that Reelin ensures the proper formation of the cerebral cortical layer structure by transiently strengthening N-cadherin-dependent adhesion between migrating neurons. Reelin is known to be associated with various neuropsychiatric disorders, such as schizophrenia, and it is possible that it is related to the pathophysiology of these diseases.
(Yuki Matsunaga, Kazunori Nakajima, Department of Anatomy, Class of '67)
Other Published Papers
1: Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice
Cell Metabolism
24 (6):795-806; 10.1016/j.cmet.2016.09.013 DEC 13 2016
Mills Kathryn F., Yoshida Shohei, Stein Liana R., Grozio Alessia, Kubota Shunsuke, Sasaki Yo, Redpath Philip, Migaud Marie E., Apte Rajendra S., Uchida Koji, Yoshino Jun, Imai Shin-ichiro
2: Contribution of propriospinal neurons to recovery of hand dexterity after corticospinal tract lesions in monkeys
Proc Natl Acad Sci USA.
114 (3):604-609; 10.1073/pnas.1610787114 JAN 17 2017
Tohyama Takamichi, Kinoshita Masaharu, Kobayashi Kenta, Isa Kaoru, Watanabe Dai, Kobayashi Kazuto, Liu Meigen, Isa Tadashi