RXFP2-positive mesenchymal stem cells in the antlerogenic periosteum contribute to postnatal development of deer antlers

The postnatal development of secondary sexual characteristics is a highly complex process governed by diverse molecular signals and serves as a key marker of sexual maturity. Deer antlers exemplify such traits, distinguished not only by their unique ability to regenerate annually but also by their initiation in postnatal life. It is well established that the antlerogenic periosteum (AP) is the only tissue responsible for postnatal antler formation. Here, we identify a population of RXFP2-positive mesenchymal stem cells within the AP of both male and female deer that are crucial for antler development, primarily through the activation of canonical Wnt signaling. This process also relies on M2 macrophages recruited via IL-34 secretion. Furthermore, these cells exhibit reduced expression of HOX genes, suggesting a high degree of developmental plasticity. Our findings offer new insights into the molecular mechanisms underlying the postnatal development of secondary sexual characteristics, using deer antlers serving as a model system.