Understanding Osteogenesis Through Penis Bone Evolution

The exaggerated morphology, phylogenetic distribution, and potential reproductive function of the mammalian penis bone, baculum, have made it the subject of studies for centuries. Nevertheless, a detailed understanding of the evolution of the baculum is lacking. Our recent research indicates that the baculum has independently evolved 9 times and been lost at least 10 times, while the structure that it develops in, the phallus, has a single origin. This fascinating evolutionary trend implies that pre‐cursor cells within the penis of mammals can either modify conserved developmental pathways, or have evolved novel genetic networks to gain or lose the potential to develop a baculum. Here we distinguish these two hypotheses by studying osteogenesis in femurs and genitalia of three mammal species, mice, ferrets, and rabbits. These species represent two independent gains of the baculum (mouse, ferret), and a species without a baculum (rabbit), while the femurs of all three species have a single origin. Specifically, we will isolate pre‐cursor cells from the developing penis and femur to create a transcriptional atlas of osteogenesis across the three species. Since these bones commonly develop through endochondral ossification the transcription factor Sox9 will be used as a marker for osteogenesis. Sox9 positive cells will be identified through immunochemistry, isolated using FACS sorting, and then processed for RNA sequencing. Sequencing results will be compared both between species, and between bones to provide insight not only into the genetic regulation of baculum development, but will also enrich our understanding of osteogenic regulation. Support or Funding Information This work was supported by the National Institutes of Health grant #GM098536