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iScience. 2018 Oct 26;8:148-160. doi: 10.1016/j.isci.2018.09.021. Epub 2018 Sep 28.

Netrin Signaling Defines the Regional Border in the Drosophila Visual Center.

Author information

1
Mathematical Neuroscience Unit, Institute for Frontier Science Initiative, 13-1 Takaramachi Kanazawa-shi, Ishikawa 920-8640, Japan.
2
Graduate School of Medical Sciences, 13-1 Takaramachi Kanazawa-shi, Ishikawa 920-8640, Japan.
3
School of Medical Sciences, Kanazawa University, 13-1 Takaramachi Kanazawa-shi, Ishikawa 920-8640, Japan.
4
School of Life Science and Technology, Tokyo Institute of Technology, Nagatsuta 4259, Yokohama, Kanagawa 226-8501, Japan.
5
Mathematical Neuroscience Unit, Institute for Frontier Science Initiative, 13-1 Takaramachi Kanazawa-shi, Ishikawa 920-8640, Japan; Graduate School of Medical Sciences, 13-1 Takaramachi Kanazawa-shi, Ishikawa 920-8640, Japan; School of Medical Sciences, Kanazawa University, 13-1 Takaramachi Kanazawa-shi, Ishikawa 920-8640, Japan. Electronic address: makotos@staff.kanazawa-u.ac.jp.

Abstract

The brain consists of distinct domains defined by sharp borders. So far, the mechanisms of compartmentalization of developing tissues include cell adhesion, cell repulsion, and cortical tension. These mechanisms are tightly related to molecular machineries at the cell membrane. However, we and others demonstrated that Slit, a chemorepellent, is required to establish the borders in the fly brain. Here, we demonstrate that Netrin, a classic guidance molecule, is also involved in the compartmental subdivision in the fly brain. In Netrin mutants, many cells are intermingled with cells from the adjacent ganglia penetrating the ganglion borders, resulting in disorganized compartmental subdivisions. How do these guidance molecules regulate the compartmentalization? Our mathematical model demonstrates that a simple combination of known guidance properties of Slit and Netrin is sufficient to explain their roles in boundary formation. Our results suggest that Netrin indeed regulates boundary formation in combination with Slit in vivo.

KEYWORDS:

Developmental Neuroscience; Mathematical Biosciences; Neuroscience

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