A hybrid computational model to predict chemotactic guidance of growth cones.

Iolanda Morana Roccasalvo,Silvestro Micera,Pier Nicola Sergi

doi:10.1038/srep11340

Iolanda Morana Roccasalvo, Silvestro Micera + Show 1 more

Open Access

https://doi.org/10.1038/srep11340

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Abstract

The overall strategy used by growing axons to find their correct paths during the nervous system development is not yet completely understood. Indeed, some emergent and counterintuitive phenomena were recently described during axon pathfinding in presence of chemical gradients. Here, a novel computational model is presented together with its ability to reproduce both regular and counterintuitive axonal behaviours. In this model, the key role of intracellular calcium was phenomenologically modelled through a non standard Gierer-Meinhardt system, as a crucial factor influencing the growth cone behaviour both in regular and complex conditions. This model was able to explicitly reproduce neuritic paths accounting for the complex interplay between extracellular and intracellular environments, through the sensing capability of the growth cone. The reliability of this approach was proven by using quantitative metrics, numerically supporting the similarity between in silico and biological results in regular conditions (control and attraction). Finally, the model was able to qualitatively predict emergent and counterintuitive phenomena resulting from complex boundary conditions.

Highlights

The overall strategy used by growing axons to find their correct paths during the nervous system development is not yet completely understood
The growth cone7 (GC) can sense diffusible gradients and move toward secretive targets[8,9,10,11,12] through a chemotactic guidance process, which involves the amplification of external chemical signals through an internal transduction process[11,13]
This phenomenological approach accounted for the intracellular calcium dynamics, as resulting from interactions with extracellular cues and random fluctuations inside the GC domain

Summary

Introduction

The overall strategy used by growing axons to find their correct paths during the nervous system development is not yet completely understood. A novel computational model is presented together with its ability to reproduce both regular and counterintuitive axonal behaviours In this model, the key role of intracellular calcium was phenomenologically modelled through a non standard Gierer-Meinhardt system, as a crucial factor influencing the growth cone behaviour both in regular and complex conditions. The key role of intracellular calcium was phenomenologically modelled through a non standard Gierer-Meinhardt system, as a crucial factor influencing the growth cone behaviour both in regular and complex conditions This model was able to explicitly reproduce neuritic paths accounting for the complex interplay between extracellular and intracellular environments, through the sensing capability of the growth cone. Since intracellular and extracellular [Ca2+] influence each other, the GC membrane likely plays an important role in axonal steering, through the dynamics of surface receptors[22]

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