Author Contributions Takumi Suzuki, C. Discussion The brain is subdivided into multiple distinct regions that consist of many different types of neurons, and each region plays unique roles to carry out complex high-order functions. OPC-NBs red produce medulla neurons in a linear and radial orientation toward the center of medulla green, small arrows. The white dotted lines encircle the area in which the degree of overlap is less than 1. Skeath, Iris Salecker, S. We also observed Fra protein localization in the lamina glial cells data not shown. We tested the robustness of this result in different parameter sets for migration speed, diffusion speed, and degree of attraction and repulsion by plotting the degree of overlap and the distance between neuron and glia Figures 4 H and 4I.

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Lawrence Zipursky, and Yuh-Nung Jan for antibodies and fly strains. It has been demonstrated that Unc5 is able to regulate repulsion in the absence of Ipx in the fly embryonic nervous system Keleman and Dickson, Introduction Compartmental subdivision of the brain into each unique region is essential for the development and function of the brain. Articles from iScience are provided here courtesy of Elsevier. Netrins guide Drosophila commissural axons at short range.

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This assumption needs to be validated in the future study. Examined sample numbers are shown at the bottom. It is possible that the disordered distribution of lamina glial cells causes the failure of the compartmental subdivision. In addition, lamina glia-specific knockdown of unc5 caused the similar boundary defects Figures 3 J—3L. Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system. F and G Boundary formation by dual action of Netrin.


Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord. When the glial cell iipc is distant from the neuron cluster, glia is attracted to neuron by the gradient of low Netrin concentration F.

This result suggests that the lamina glial cells are the essential sources of Slit required for the compartmental subdivision.

Medial sections showing the medulla as indicated in A1. Limitations of the Study Although we propose that a simple combination of Slit-dependent repulsion and dual functions of Netrin an attractant when its concentration is low and a repellent when i;c concentration is high is sufficient to explain their roles in boundary formation, our mathematical model ipd very simplified from the real phenomenon found in the fly brain.

First, we examined the localization patterns of the ligands NetA and NetB. Netrin1 produced by neural progenitors, not floor plate cells, is required for axon guidance in the spinal cord.

Localized netrins act as positional cues to control 8460 targeting of photoreceptor axons in Drosophila. Here, we define that the two clusters of cells form a sharp boundary when their overlap and distance are sufficiently small. The invasion of IPC cells equally occurred in the ventral, dorsal, and central part of the brain.

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Floor-plate-derived netrin-1 is dispensable for commissural axon guidance. Nevertheless, Netrin and Slit pathways are broadly conserved from invertebrates to vertebrates. Here, we show that Netrin signaling, another axon guidance signaling pathway, regulates the formation of the border between the OPC and IPC.


Compartmental subdivision of the brain into each unique region is essential for the development and function of the brain. 860 mathematical model demonstrates that a simple combination of known guidance properties of Slit and Netrin is sufficient to explain their roles in boundary formation. In addition, it was shown that Netrin signaling is not required for long-range attraction but promotes adhesion to the target layer Akin and Zipursky, Similar defects were observed in unc5 null mutant brains Figures 2 D and 2R.

Since these signaling pathways are evolutionarily conserved from insects to mammals, their roles in establishing the tissue border may also be conserved across species. In the first test, the speed of cell migration and ligand diffusion lpc changed 0. We examined the effects of these early defects on the structure of the adult optic lobe. Click here to view.

We initially compared the difference between the following three conditions, Netrin is an attractant, repellent, and both. Thus, these results suggest that Netrin signaling controls the distribution of glial cells. Formation of neuronal circuits by interactions between neuronal populations derived from different origins in the Drosophila visual center.