Exploring the mechanisms regulating regeneration of deer antlers

Abstract

Deer antlers are the only mammalian appendages capable of repeated rounds of regeneration; every year they are shed and regrow from a blastema into large branched structures of cartilage and bone that are used for fighting and display. Longitudinal growth is by a process of modified endochondral ossification and in some species this can exceed 2 cm per day, representing the fastest rate of organ growth in the animal kingdom. However, despite their value as a unique model of mammalian regeneration the underlying mechanisms remain poorly understood. We review what is currently known about the local and systemic regulation of antler regeneration and some of the many unsolved questions of antler physiology are discussed. Molecules that we have identified as having potentially important local roles in antlers include parathyroid hormone-related peptide and retinoic acid (RA). Both are present in the blastema and in the rapidly growing antler where they regulate the differentiation of chondrocytes, osteoblasts and osteoclasts in vitro. Recent studies have shown that blockade of RA signalling can alter cellular differentiation in the blastema in vivo. The trigger that regulates the expression of these local signals is likely to be changing levels of sex steroids because the process of antler regeneration is linked to the reproductive cycle. The natural assumption has been that the most important hormone is testosterone, however, at a cellular level oestrogen may be a more significant regulator. Our data suggest that exogenous oestrogen acts as a 'brake', inhibiting the proliferation of progenitor cells in the antler tip while stimulating their differentiation, thus inhibiting continued growth. Deciphering the mechanism(s) by which sex steroids regulate cell-cycle progression and cellular differentiation in antlers may help to address why regeneration is limited in other mammalian tissues.

Stem cell options for kidney disease

“…Many studies have shown that genes implicated in early embryonic development are reactivated during blastema formation in zebrafish [106][107][108][109][110] and amphibians [111,112]. In a mammalian context, there is a marked overlap between the molecular mechanisms that control maintenance of the antler progenitor cells and developmental pathways in regenerating deer antlers [113,114]. Deer antlers are the only mammalian organ capable of complete epimorphic regeneration and so may become an important model for mammalian tissue regeneration [115,116].…”

Antler velvet is thicker in adult than in yearling pampas deer (Ozotoceros bezoarticus): a histological study

“…Antler nerves grow through the velvet in close association to blood vessels in an environment rich in growth promoting molecules [20]. The AV is shed in coincidence with a great increase in testosterone concentration occurring before the rut onset [19,21].…”

Hurt yourself to hurt your enemy: new insights on the function of the bizarre antipredator mechanism in the salamandridPleurodeles waltl

“…Gonyea & Ashworth, 1975;Blackburn, Hanken & Jenkins Jr, 2008) and horns or antlers (e.g. CluttonBrock, 1982;Price & Allen, 2004). The use of ribs as 'concealed' weapons, however, is known only from two phylogenetically closely related salamander genera: Pleurodeles and Echinotriton (Leydig, 1879;Nowak & Brodie Jr, 1978;Brodie Jr, 1983;Brodie Jr et al, 1984).…”