Dataset Information

Multi-phasic bi-directional chemotactic responses of the growth cone.

ABSTRACT: The nerve growth cone is bi-directionally attracted and repelled by the same cue molecules depending on the situations, while other non-neural chemotactic cells usually show uni-directional attraction or repulsion toward their specific cue molecules. However, how the growth cone differs from other non-neural cells remains unclear. Toward this question, we developed a theory for describing chemotactic response based on a mathematical model of intracellular signaling of activator and inhibitor. Our theory was first able to clarify the conditions of attraction and repulsion, which are determined by balance between activator and inhibitor, and the conditions of uni- and bi-directional responses, which are determined by dose-response profiles of activator and inhibitor to the guidance cue. With biologically realistic sigmoidal dose-responses, our model predicted tri-phasic turning response depending on intracellular Ca²⁺ level, which was then experimentally confirmed by growth cone turning assays and Ca²⁺ imaging. Furthermore, we took a reverse-engineering analysis to identify balanced regulation between CaMKII (activator) and PP1 (inhibitor) and then the model performance was validated by reproducing turning assays with inhibitions of CaMKII and PP1. Thus, our study implies that the balance between activator and inhibitor underlies the multi-phasic bi-directional turning response of the growth cone.

SUBMITTER: Naoki H

PROVIDER: S-EPMC5093620 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Multi-phasic bi-directional chemotactic responses of the growth cone.

Naoki Honda H Nishiyama Makoto M Togashi Kazunobu K Igarashi Yasunobu Y Hong Kyonsoo K Ishii Shin S

Scientific reports 20161103

The nerve growth cone is bi-directionally attracted and repelled by the same cue molecules depending on the situations, while other non-neural chemotactic cells usually show uni-directional attraction or repulsion toward their specific cue molecules. However, how the growth cone differs from other non-neural cells remains unclear. Toward this question, we developed a theory for describing chemotactic response based on a mathematical model of intracellular signaling of activator and inhibitor. Ou ...[more]

PMID: 27808115

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Dataset Information

Multi-phasic bi-directional chemotactic responses of the growth cone.

Publications

Multi-phasic bi-directional chemotactic responses of the growth cone.

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