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Title: Mutual inhibition among neighbouring neurons regulates axonal target choice and robustness of developing brain maps
Other Titles: Mutuele inhibitie tussen aangrenzende neuronen reguleren axonale doelwitkeuze en robuustheid tijdens de ontwikkeling van het hersennetwerk
Authors: Langen, Marion
Issue Date: 14-May-2012
Abstract: During brain development, axons of neighbouring neurons navigate long distances in a complex and contradictory environment of guidance cues and morphogen signals to make differential connectivity decisions and generate functional brain circuits. Such maps display a high degree of accuracy and reproducibility across individuals, hinting at mechanisms that ensure robustness of neuronal wiring in the face of environmental and genetic variation. The identities and properties of these robustness mechanisms, whether they are genetically encoded and how they interact with axon guidance cues are unknown. Using quantitative anatomy, genetics and mathematical modelling approaches we provide evidence that mutual inhibition between neighbouring postmitotic neurons via Notch signalling imparts developmental plasticity and robustness upon developing neuronal circuits. First, we generate a quantitative anatomical description for a set of Drosophila melanogaster CNS visual system neurons. Next, we use genetic approaches to show that small subsets of neighbouring neurons communicate with each other during axonal outgrowth to generate alternative, high versus low, states of Notch activity. Furthermore, Notch activity levels attenuate a neuron's response to axon guidance signals, allowing neurons to make alternative and mutually exclusive axon target choices. Loss of Notch activity in a given neuron autonomously alters it's axon target choice. However, because neighbouring cells then adopt the alternative choice, the overall normal connectivity pattern is preserved. Mathematical modelling shows that mutual inhibition during axon outgrowth is a form of developmental plasticity that generates a very high degree of robustness in neuronal wiring.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Department of Human Genetics - miscellaneous
Laboratory of Neurogenetics

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