Delayed neuronal maturation in humans

Since the split of Homo sapiens from the last common nonhuman primate (NHP) ancestor, the human brain has substantially altered its size, structure, and connectivity. The human brain has a larger mass with respect to body weight, increased cortical neurons with respect to size, an expanded proliferative zone, and unique connectivity patterns. Human neurons exhibit an exceptionally delayed time course, exhibiting more mature characteristics after a prolonged time compared to other primates, a characteristic termed neoteny. It is hypothesized that this longer developmental period plays a role in the aforementioned structural and connectivity differences. It has long been proposed that the phenotypic differences between closely related species may be driven, in part, by divergent transcriptional regulation rather than by novel protein-coding sequence, given the extensive conservation of the protein coding DNA sequences in the primate lineage. However, how these regulatory mechanisms play a role in the protracted maturation process in human neurons remains largely unknown. In this lecture, we will discuss molecular factors that can contribute to the prolonged maturation of human neurons compared to other primates and the impact on human development and neurodevelopmental diseases.