Journal
ISCIENCE
Volume 8, Issue -, Pages 148-+Publisher
CELL PRESS
DOI: 10.1016/j.isci.2018.09.021
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Funding
- CREST from JST [JPMJCR14D3]
- MEXT [JP17H05739, JP17H05761, JP17H03542, JP18H05099, JP26291047, JP16H06457, JP18K06250]
- Sekisui Chemical Grant Program
- Asahi Glass Foundation
- Takeda Science Foundation
- Cooperative Research of 'Network Joint Research Center for Materials and Devices'
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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.
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