Physical understanding of axonal growth patterns on grooved substrates:groove ridge crossing versus longitudinal alignment

Surface topographies such as micrometric edges and grooves have been widely used to improve neuron outgrowth.However,finding the mechanism of neuron–surface interactions on grooved substrates remains a challenge.In this work,PC12 cells and chick forebrain neurons(CFNs)were cultured on grooved and smooth polyacrylonitrile substrates.It was found that CFNs showed a tendency of growing across groove ridges;while PC12 cells were only observed to grow in the longitudinal direction of grooves.To further investigate these observations,a 3D physical model of axonal outgrowth was developed.In this model,axon shafts are simulated as elastic 3D beams,accounting for the axon outgrowth as well as the focal contacts between axons and substrates.Moreover,the bending direction of axon tips during groove ridge crossing is governed by the energy minimization principle.Our physical model predicts that axonal groove ridge crossing is contributed by the bending compliance of axons,caused by lower Young’s modulus and smaller diameters.This work will aid the understanding of the mechanisms involved in axonal alignment and elongation of neurons guided by grooved substrates,and the obtained insights can be used to enhance the design of instructive scaffolds for nerve tissue engineering and regeneration applications.

Proteoglycans: Road Signs for Neurite Outgrowth

Proteoglycans in the central nervous system play integral roles as ＂traffic signals＂ for the direction of neurite outgrowth. This attribute of proteoglycans is a major factor in regeneration of the injured central nervous system. In this review, the structures of proteoglycans and the evidence suggesting their involvement in the response following spinal cord injury are presented. The review further describes the methods routinely used to determine the effect proteoglycans have on neurite outgrowth. The effects of proteoglycans on neurite outgrowth are not completely understood as there is disagreement on what component of the molecule is interacting with growing neurites and this ambiguity is chronicled in an historical context. Finally, the most recent findings suggesting possible receptors, interactions, and sulfation patterns that may be important in eliciting the effect of proteoglycans on neurite outgrowth are discussed. A greater understanding of the proteoglycan-neurite interaction is necessary for successfully promoting regeneration in the iniured central nervous system.

RACK1 regulates neural development

Receptor for activated C kinase 1（RACK1）is an evolutionarily conserved scaffolding protein within the tryptophan-aspartate（WD）repeat family of proteins.RACK1 can bind multiple signaling molecules concurrently,as well as stabilize and anchor proteins.RACK1 also plays an important role at focal adhesions,where it acts to regulate cell migration.In addition,RACK1 is a ribosomal binding protein and thus,regulates translation.Despite these numerous functions,little is known about how RACK1 regulates nervous system development.Here,we review three studies that examine the role of RACK1 in neural development.In brief,these papers demonstrate that（1）RACK-1,the C.elegans homolog of mammalian RACK1,is required for axon guidance;（2）RACK1 is required for neurite extension of neuronally differentiated rat PC12cells;and（3）RACK1 is required for axon outgrowth of primary mouse cortical neurons.Thus,it is evident that RACK1 is critical for appropriate neural development in a wide range of species,and future discoveries could reveal whether RACK1 and its signaling partners are potential targets for treatment of neurodevelopmental disorders or a therapeutic approach for axonal regeneration.