Distribution of BDNF and TrkB isoforms in growing antler tissues of red deer

Abstract

Antlers are the cranial appendages of deer that regenerate each year. This renewal provides a model to explore molecules involved in mammalian organ regeneration.The cellular distributions of the brain-derived neurotrophic factor (BDNF) and the isoforms of its cognate receptor Trk tyrosine kinase receptor (TrkB) were localized by immunohistochemistry in sections of growing red deer antler. BDNF and TrkB full length were widely expressed in the integument, perichondrium, periosteum and bone. The truncated isoform receptor was particularly evidenced in integument and vascular inner dermis, but very light reaction was observed in cartilage and bone, both at the site of endochondral and intramembranous ossification. These observations were also assessed at transcriptional level by RT-PCR analyses. The highest expression of all genes significantly occurred in chondroprogenitor cells; however the full-length TrkB receptor was down regulated in osteocartilaginous compartments, in which the truncated isoform was up regulated. The truncated isoform is a dominant-negative receptor that inhibits the full length receptor signalling, even if the truncated isoform not only has this function.This study establishes the presence of BDNF and its receptor in the different cellular compartments of growing antler. Their transcripts assessed by RT-PCR indicate a local synthesis of these molecules that may contribute to the modulation of antler growth, acting as autocrine and/or paracrine factors independently of nerve supply. Among the plethora of other molecular signals and growth factors affecting the antler growth, the local production of BDNF and its cognate receptor could be of interest in understanding their role in antler renewal and to delineate the different involvement of the receptor isoforms.