Unlocking the mysteries of human cognition and evolution, neurobiologists have long sought to decipher the enigmatic role of the neocortex—the seat of abstract thought, artistic expression, and linguistic prowess—in defining our humanity. In a landmark study published in the EMBO Journal, Dr. Mareike Albert and an international team from the Center for Regenerative Therapies Dresden (CRTD) at TUD Dresden University of Technology have illuminated a novel factor implicated in the expansion of the human neocortex.
The neocortex, akin to a folded walnut, distinguishes humans and primates with its characteristic convolutions, augmenting the surface area critical for higher cognitive functions. Dr. Albert elucidates, “The neocortex is the most recently evolved part of the brain,” underscoring its pivotal role in shaping human cognition. While all mammals possess a neocortex, variations in size and complexity underscore evolutionary distinctions, with humans and primates boasting folds absent in their rodent counterparts.
Yet, the molecular mechanisms driving neocortex evolution remain elusive. Dr. Albert posits, “Which genes are responsible for inter-species differences in neocortex size? What factors have contributed to brain expansion in humans?” Addressing these questions holds profound implications for understanding human brain development and addressing neurological disorders.
Leveraging the power of brain organoids—three-dimensional cell cultures that mimic the cellular complexity of developing brains—the research team embarked on a comparative analysis of developing mouse and human brains. Stemming from the revelation that humans harbor an expanded pool of stem cells during brain development, the team identified a human-specific factor absent in mice: epiregulin.
Through meticulous experimentation with brain organoids, the team unveiled epiregulin’s pivotal role in promoting the division and expansion of human neocortical stem cells. Yet, the evolutionary journey of epiregulin proved equally enlightening. While not exclusive to humans, epiregulin’s dosage emerged as a critical determinant of neocortical expansion across species.
Intriguingly, the team’s exploration extended to gorilla brain organoids, offering insights into brain development in endangered species without direct interaction. Comparing the effects of epiregulin in human and gorilla brain organoids, the team discerned nuanced differences in its impact, underscoring the regulatory influence of epiregulin dosage on neocortical expansion.
In a remarkable conclusion, Dr. Albert asserts, “Unlike previously identified factors, epiregulin as such seems not to be unique to humans. Instead, the amount of the growth factor seems to be the crucial regulator for the inter-species differences.” This revelation not only enhances our understanding of human uniqueness but also underscores the significance of ethical and non-invasive approaches, such as organoid research, in complementing traditional animal studies.
In unveiling the intricate interplay of genetic and environmental factors shaping human cognition, this groundbreaking study illuminates new avenues for exploring the evolutionary underpinnings of human intelligence and the potential therapeutic avenues for neurological disorders.