Sep 15, 2020

Elucidating the mechanisms for newborn neurons' departure
~ The DSCAM protein slices off the legs of the neurons attached to the ventricular surface. ~

A research group led by Dr. Nariko Arimura, Research Fellow and Dr. Mikio Hoshino, at National Center of Neurology and Psychiatry (NCNP), has revealed that the DSCAM protein has the ability to detach the endfoot adhesions of neurons from the ventricular surface of the brain. It is only when this adhesion is removed that the neurons begin to migrate and arrive at the designated location. Impairment of this process occasionally causes various neuropsychiatric illnesses, such as neurodevelopmental disorders and epilepsy. However, the molecular mechanism by which this "endfoot detachment", the earliest stage of neuronal development, is regulated has not been well understood.

Our research group have found that DSCAM protein becomes enriched in the endfeet of neurons in the midbrain during brain development, and that inhibition of DSCAM function prevents the endfoot detachment from the ventricular surface, which indicates DSCAM is involved in the endfoot detachment process. Furthermore, various analyses have revealed that DSCAM protein promotes endfoot detachment by binding to RAPGEF2 protein, which reduces the activity of RAP1 protein and the amount of the cell adhesion molecule, N-cadherin, that maintains endfoot adhesion. This study not only elucidates the molecular mechanisms of the earliest stage of neuronal development, but also provides insights into the various neurodevelopmental disorders caused by this important developmental process.

The findings were published in the online edition of the scientific journal Science Advances.

Arimura N, Okada M, Taya S, Dewa KI, Tsuzuki A, Uetake H, Miyashita S, Hashizume K, Shimaoka K, Egusa S, Nishioka T, Yanagawa Y, Yamakawa K, Inoue YU, Inoue T, Kaibuchi K, Hoshino M: DSCAM regulates delamination of neurons in the developing midbrain. Science Advances, 2020, 6 (36): eaba1693
DOI: 10.1126/sciadv.aba1693

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