Oscillations in a neurite growth model with extracellular feedback

V.I Mironov,A.S Romanov,A.Yu Simonov,M.V Vedunova,V.B Kazantsev

doi:10.1016/j.neulet.2014.03.041

V.I Mironov, A.S Romanov + Show 3 more

Open Access

https://doi.org/10.1016/j.neulet.2014.03.041

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Abstract

We consider the influence of extracellular signalling on neurite elongation in a model of neurite growth mediated by building proteins (e.g., tubulin). The tubulin production dynamics were supplied by a function describing the influence of extracellular signalling, which can promote or depress neurite elongation. We found that this extracellular feedback could generate neurite length oscillations consisting of a periodic sequence of elongations and retractions. The oscillations prevent further outgrowth of the neurite, which becomes trapped in the non-uniform extracellular field. We analysed the characteristics of the elongation process for different distributions of attracting and repelling sources of the extracellular signalling molecules. The model predicts three different scenarios of neurite development in the extracellular field, including monotonic and oscillatory outgrowth, localised limit cycle oscillations and complete growth depression.

Highlights

Neural development and dendritic morphogenesis underlie formation of specific network structures, synaptic connectivity and information processing in the brain[1,2,3,4].Abnormalities in neuronal development and regeneration are implicated in several neurological disorders such as autism, schizophrenia and epilepsy[5,6,7,8,9].Generation of certain morphological patterns involves complex intracellular molecular cascades modulated by extracellular signaling
First we consider two different distributions of growth factor sources (Fig. 2 A and B) and chose the direction of the neurite growth shown by arrows
The amplitude of the fluctuation decreased and when the neurite enters the region with a positive extracellular signal, it promoted the tubulin production and neurite growth is continued

Summary

Introduction

Neural development and dendritic morphogenesis underlie formation of specific network structures, synaptic connectivity and information processing in the brain[1,2,3,4].Abnormalities in neuronal development and regeneration are implicated in several neurological disorders such as autism, schizophrenia and epilepsy[5,6,7,8,9].Generation of certain morphological patterns involves complex intracellular molecular cascades modulated by extracellular signaling. Neurite elongation and branching provide the formation of certain dendritic patterns guided by extracellular growth factor molecules released by the other cells. An inverse process called retraction is important fordevelopment and functioning of the nervous system It may be caused by lysophosphatidic acid [13], some types of signaling molecules such as semaphorins, netrins, and ephrins[14,15], glutamate[16] and other[17]. The elongation process depends on building proteins (e.g. tubulin, actin) produced in cell soma. Those proteins are transported to the growth cone by diffusion and active transport, assembled in microtubules providing elongation of the neurite. The growth can be influenced by many factors including cell adhesion, binding to extracellular matrix components[18,19]

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