Nerve Growth Factor mRNA Expression in the Regenerating Antler Tip of Red Deer (Cervus elaphus)

Abstract

Deer antlers are the only mammalian organs that can fully regenerate each year. During their growth phase, antlers of red deer extend at a rate of approximately 10 mm/day, a growth rate matched by the antler nerves. It was demonstrated in a previous study that extracts from deer velvet antler can promote neurite outgrowth from neural explants, suggesting a possible role for Nerve Growth Factor (NGF) in antler innervation. Here we showed using the techniques of Northern blot analysis, denervation, immunohistochemistry and in situ hybridization that NGF mRNA was expressed in the regenerating antler, principally in the smooth muscle of the arteries and arterioles of the growing antler tip. Regenerating axons followed the route of the major blood vessels, located at the interface between the dermis and the reserve mesenchyme of the antler. Denervation experiments suggested a causal relationship exists between NGF mRNA expression in arterial smooth muscle and sensory axons in the antler tip. We hypothesize that NGF expressed in the smooth muscle of the arteries and arterioles promotes and maintains antler angiogenesis and this role positions NGF ahead of axons during antler growth. As a result, NGF can serve a second role, attracting sensory axons into the antler, and thus it can provide a guidance cue to define the nerve track. This would explain the phenomenon whereby re-innervation of the regenerating antler follows vascular ingrowth. The annual growth of deer antler presents a unique opportunity to better understand the factors involved in rapid nerve regeneration.

NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone

“…In contrast to the large body of literature on the role of peripheral nerves in the development of other tissues (Kumar and Brockes, 2012; Li et al, 2007), relatively few studies have investigated the function of peripheral nerves in the developing skeleton. Primary afferent sensory and sympathetic axons are known to cover the entire periosteal bone surface, are present in mineralized bone at the regions of highest metabolic activity, and reach deep into the marrow space (Bjurholm et al, 1988; Hill and Elde, 1991; Hukkanen et al, 1992; Mach et al, 2002; Wojtys et al, 1990).…”

The effect of deer antler growth factor on the viability and proliferation of primary human alveolar osteoblast cells in vitro

“…To investigate the cascade of events leading to rapid growth and osteogenic activity, current research has focused on identifying and characterizing trophic factors present in the regeneration phase of this organ. Besides, the effects of hormones, growth factors such as insulin-like growth factor, epidermal growth factor, vascular endothelial growth factor, nerve growth factor, as well as bone morphogenetic proteins, have been shown to play important roles in regeneration processes of deer antler [1,4,10,15,17].…”

Antler regrowth as a form of epimorphic regeneration in vertebrates - a comparative view

“…The sympathetic supply of the pedicle is derived from the second cervical nerve, while the antler normally lacks a sympathetic innervation, except for (long-lived) antlers of castrates (114). There is evidence that nerve growth factor (NGF) promotes the outgrowth of the nerve fibers of the regenerating antler (115,116) and it has been suggested that NGF produced by smooth muscles of arteries and arterioles provides a guidance cue defining the track followed by the outgrowing nerve fibers (115). However, also other as yet unidentified molecules appear to be involved in promoting nerve fiber growth (116).…”