Regulation of nerve growth and patterning by cell surface protein disulphide isomerase

Abstract

Contact repulsion of growing axons is an essential mechanism for spinal nerve patterning. In birds and mammals the embryonic somites generate a linear series of impenetrable barriers, forcing axon growth cones to traverse one half of each somite as they extend towards their body targets. This study shows that protein disulphide isomerase provides a key component of these barriers, mediating contact repulsion at the cell surface in chick half-somites. Repulsion is reduced both in vivo and in vitro by a range of methods that inhibit enzyme activity. The activity is critical in initiating a nitric oxide/S-nitrosylation-dependent signal transduction pathway that regulates the growth cone cytoskeleton. Rat forebrain grey matter extracts contain a similar activity, and the enzyme is expressed at the surface of cultured human astrocytic cells and rat cortical astrocytes. We suggest this system is co-opted in the brain to counteract and regulate aberrant nerve terminal growth.

Axons in the Chick Embryo Follow Soft Pathways Through Developing Somite Segments

“…Several canonical guidance molecules participate in the segmentation of motor axon outgrowth, while not fully accounting per se for the segmentation process in the developing spinal cord (Koblar et al, 2000;Huber et al, 2005;Roffers-Agarwal and Gammill, 2009). Recently, the identity of a peanut agglutinin-binding protein has been unraveled as cell surface protein disulfide isomerase (PDI), which mediates the contact-repulsion mechanism of posterior half-sclerotomes (Cook et al, 2020). However, alongside chemical signalling, mechanical signals may also participate in the joint ingrowth of spinal axons into the anterior halfsegment while avoiding the posterior segment.…”

System for Patterning Polydopamine and VAPG Peptide on Polytetrafluoroethylene and Biodegradable Polyesters for Patterned Growth of Smooth Muscle Cells In Vitro

“…This should be achieved on the surface of biocompatible or biodegradable grafts, prostheses, or scaffolds used to repair or regenerate damaged tissues . The guided alignment of the cells is critical in cultures of muscle and nerve cells, for which biological functionality strongly depends on the proper organization in tissues, which is precisely regulated in organisms. − …”

“… 17 The guided alignment of the cells is critical in cultures of muscle and nerve cells, for which biological functionality strongly depends on the proper organization in tissues, which is precisely regulated in organisms. 18 − 21 …”