Sox9 Functions as a Master Regulator of Antler Growth by Controlling Multiple Cell Lineages

Deer antlers are amazing natural appendages that grow faster than any other known mammalian bone. Antler growth occurs at the tip and is initially cartilage, which is later replaced by bone tissue. However, little is known regarding the precise role of cooperation between cell lineages and functional genes in regulating antler growth, and molecular mechanisms responsible for rapid growth remain elusive. In this study, we use an RNA-Seq approach to elucidate the full spectrum of cell lineages, functional genes, and their cooperative interactions during antler growth. We identify Sox9 as a pivotal transcription factor during chondrogenesis and skeletal development expressed in the chondrocyte lineage from the multipotent mesenchymal precursor stage through most subsequent cell differentiation stages with a particularly strong activity in proliferating and prehypertrophic chondrocytes. Furthermore, we analyze the miRNA expression patterns at initial growth stage and rapid growth stage and identify several miRNAs that involve in regulating antler chondrogenesis and rapid growth. Among these miRNAs, miR-140 plays pivotal role during antler growth by targeting Sox9 and vice versa.