GLI3 in Archaic Humans: Possible Contributions to Human Skeletal and Brain Evolution

Neanderthals, an extinct hominid, lived in Eurasia until about 40,000 years ago. According to fossils, Neanderthals had distinctive anatomical features compared to modern humans, including a long front-to-back cranium, low frontal bones, and strong skeletal formation. Furthermore, Neanderthals had large brains similar to those of modern humans, but their brain morphology was different from ours, suggesting that they had different cognitive abilities than modern humans. Recent archaic human genome analysis has unveiled genetic changes underlying Neanderthals' or modern human-specific anatomical and physiological traits. In this review, we focus on the role of GLI3, a key molecule that mediates Hedgehog signaling during vertebrate organogenesis. We discuss possible contributions of GLI3-mediated hedgehog signaling to human anatomical diversifications, including neocortical structures, which provide insights into the genetic and developmental bases for modern human evolution.