Netrin Signaling Defines the Regional Border in the Drosophila Visual Center

Takumi Suzuki,Chuyan Liu,Satoru Kato,Kohei Nishimura,Hiroki Takechi,Tetsuo Yasugi,Rie Takayama,Satoko Hakeda-Suzuki,Takashi Suzuki,Makoto Sato

doi:10.1016/j.isci.2018.09.021

Takumi Suzuki, Chuyan Liu + Show 8 more

Open Access

https://doi.org/10.1016/j.isci.2018.09.021

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Abstract

SummaryThe 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.

Highlights

Compartmental subdivision of the brain into each unique region is essential for the development and function of the brain
Our model demonstrated that the guidance functions of Netrin and Slit are sufficient to explain their roles in boundary formation
To identify other regulatory signaling pathways, we conducted expression screening for typical axon guidance molecules and found that Netrin and its receptors are expressed in the medulla primordium

Summary

Introduction

Compartmental subdivision of the brain into each unique region is essential for the development and function of the brain. The established compartmental borders play crucial roles in controlling the behavior of signaling molecules that regulate cell fate as well as in isolating cells in each individual region (Kiecker and Lumsden, 2005; Batlle and Wilkinson, 2012). Border formation along each compartment is known to be regulated by three mechanisms: differential affinity in cellular adhesion, interfacial tension between different cell populations, and cell repulsion by intercellular signaling (Batlle and Wilkinson, 2012). All of these mechanisms involve molecular machineries located at the cell membrane. The mechanism of border formation by diffusible guidance molecules is only poorly understood

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