Abstract
Brain connectivity maps display a delicate balance between individual variation and stereotypy, suggesting the existence of dedicated mechanisms that simultaneously permit and limit individual variation. We show that during the development of the Drosophila central nervous system, mutual inhibition among groups of neighboring postmitotic neurons during development regulates the robustness of axon target choice in a nondeterministic neuronal circuit. Specifically, neighboring postmitotic neurons communicate through Notch signaling during axonal targeting, to ensure balanced alternative axon target choices without a corresponding change in cell fate. Loss of Notch in postmitotic neurons modulates an axon's target choice. However, because neighboring axons respond by choosing the complementary target, the stereotyped connectivity pattern is preserved. In contrast, loss of Notch in clones of neighboring postmitotic neurons results in erroneous coinnervation by multiple axons. Our observations establish mutual inhibition of axonal target choice as a robustness mechanism for brain wiring and unveil a novel cell fate independent function for canonical Notch signaling. DOI:http://dx.doi.org/10.7554/eLife.00337.001.
Highlights
Coupling axonal target choice to neuronal cell fate determination has the advantage of generating highly reproducible wiring patterns
We show that higher order central nervous system (CNS) neurons utilize mutual inhibition via Notch signaling to establish a robust wiring map
Non-parametric Kruskal–Wallis Test. (E′) Confirmation of the requirement of Notch signaling during pupation using tubGal80ts: Control 11.71 ± 0.92 SD (n = 17, non-Gaussian distribution), 24–48 hr after puparium formation (APF) 15.55 ± 1.04 SD (n = 17, non-Gaussian distribution) (p
Summary
Coupling axonal target choice to neuronal cell fate determination has the advantage of generating highly reproducible wiring patterns It has the evolutionary disadvantage of limiting individual variability, and efficient adaptation to environmental change. A strictly deterministic coupling has the significant developmental disadvantage of limiting cellular plasticity in response to inevitable genetic and epigenetic variability within the developing brain (Muotri et al, 2005, 2010). The latter point is critical in neuronal lineages that are intrinsically variable in cell number. A group of equivalent neuroepithelial cells that initially express roughly the same Notch activity are eventually segregated in two groups defined by expression and activity levels
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