MERLN Speaker Series | Luca Guglielmi
On the 25th of June at 11:00, we have the pleasure to host Luca Guglielmi from the University of Trento. He will be giving a talk titled: “Modelling Neuronal Morphogenesis Across Species: a Purkinje Cell’s Journey to Utmost Complexity”.
Modelling Neuronal Morphogenesis Across Species: a Purkinje Cell’s Journey to Utmost Complexity
Human brain development is exceptionally slow and correlates with the remarkable size and complexity of human neurons. This is particularly striking in the cerebellum, where Purkinje cells form disproportionate dendritic arbors. However, how prolonged development translates into increased neuronal size and complexity remains unclear. By combining self-organization with guided differentiation, we established human air–liquid interface cerebellar organoids that recapitulate human developmental timing and generate Purkinje cells undergoing discrete, in vivo-like morphogenetic transitions, culminating in polarized dendritic arbors. Through cross-species comparisons in vitro, we find that the growth rate of human Purkinje cells is slower than that of mice; however, they spend disproportionately longer in successive morphogenetic states, ultimately reaching larger sizes. In contrast, in the closely related primate cynomolgus macaque, growth rate and the duration of morphogenetic transitions appear to be delayed proportionally, resulting in neuronal sizes closer to those of mice than humans. We propose that a selective uncoupling between these parameters during neuronal maturation represents a hominid-specific mechanism underlying the exceptional size and complexity of human neurons.