Do you have the nerves to regenerate? The importance of neural signalling in the regeneration process

Abstract

The importance of nerve-derived signalling for correct regeneration has been the topic of research for more than a hundred years, but we are just beginning to identify the underlying molecular pathways of this process. Within the current review, we attempt to provide an extensive overview of the neural influences during early and late phases of both vertebrate and invertebrate regeneration. In general, denervation impairs limb regeneration, but the presence of nerves is not essential for the regeneration of aneurogenic extremities. This observation led to the "neurotrophic factor(s) hypothesis", which states that certain trophic factors produced by the nerves are necessary for proper regeneration. Possible neuron-derived factors which regulate regeneration as well as the denervation-affected processes are discussed.

Mechanisms of urodele limb regeneration

“…Nerves have long been recognized as the electrical system of the body, but their role in niche support for stem cells of various organs, for regulation of wound repair, and for cell proliferation in amphibian limb regeneration is of more recent recognition (Kumar & Brockes, 2012; Pirotte, Leynen, Artois, & Smeets, 2015). …”

Zebrafish fin and heart: what's special about regeneration?

“…An intriguing regeneration-specific process is the requirement of nerves for regeneration, but not development, which was recognized for salamander limbs decades ago [73,74]. Both sensory and motor neurons can support regeneration independent of electrical activity, indicating that they release factors required for regeneration [73].…”

Regulation of dorso-ventral polarity by the nerve cord during annelid regeneration: A review of experimental evidence

“…Placing the annelid data reviewed here in the context of studies performed in other animals reveals several common elements. Most broadly, the studies reviewed here point to a central role for the nervous system in regeneration in annelids, as has been indicated for regeneration in a range of other animals (Kumar & Brockes, ; Pirotte et al., ). Another important common finding is that a DV discontinuity elicits body outgrowths.…”

“…The experiments just described suggest that ventral tissues may be particularly important in conferring proper blastema patterning. The presence of the ventral nerve cord is one of the most significant differences between ventral and dorsal tissues, and innervation has long been implicated in regeneration in a wide range of animals (Kumar & Brockes, ; Pirotte, Leynen, Artois, & Smeets, ). For these reasons, the role of the ventral nerve cord in DV patterning and regeneration during caudal regeneration was investigated further in nereids.…”

“…icant differences between ventral and dorsal tissues, and innervation has long been implicated in regeneration in a wide range of animals(Kumar & Brockes, 2012;Pirotte, Leynen, Artois, & Smeets, 2016). For these reasons, the role of the ventral nerve cord in DV Regeneration at wound sites with and without the intestine present in the nereid Nereis pelagica.…”