Uncovering New Insights Into Primate Brain Evolution

In a recent research investigation, scientists from Yale University unveiled the molecular pathways responsible for the developmental distinctions that set primates apart from mice.

The brain's development relies on a complex, highly orchestrated sequence of events initiated by neural stem cells, which give rise to increasingly specialized cells responsible for various brain functions. However, what specific molecular events drive these differences between primate and mouse brains during this process?

In a recent investigation, Yale scientists employed brain organoids, which are miniature three-dimensional models of developing brains, to monitor alterations brought about by neural stem cells in the brains of macaque monkeys and humans.

By comparing these results with knowledge gleaned from previous mouse brain studies, they unveiled the molecular foundations behind the developmental distinctions that set primates apart from mice.

One of the notable distinctions they noted was the heightened activation of GALP (Galanin-like peptide) in the brains of macaques and humans. This peptide had previously been associated with energy metabolism and appetite regulation.

The study findings were reported in the journal Science.

It is important to understand how primate brains develop and where higher cognitive functions come from.”

Nicola Micali, Study Co-First Author and Associate Research Scientist, Yale University

Nicola Micali works in the lab of Pasko Rakic, the Dorys McConnell Duberg Professor of Neuroscience and Professor of Neurology, School of Medicine,

Analysis of brain organoids generated from pluripotent stem cells of both humans and monkeys revealed that GALP played a role in promoting the proliferation of neural stem cells in primate brains, as reported by the researchers. In contrast, no similar GALP-induced activity was observed in the mouse brain.

The finding suggests that GALP may play a role in the increased size and complexity of the primate brain across evolution.”

Nicola Micali, Study Co-First Author and Associate Research Scientist, Yale University

Furthermore, the scientists identified genes within neural stem cells that have been associated with neuropsychiatric disorders, including conditions like schizophrenia and bipolar disorder, at a very early stage of fetal brain development.

This suggests the origins of these diseases occur much earlier in development than we had thought.”

Nicola Micali, Study Co-First Author and Associate Research Scientist, Yale University

The publication was one of 21 papers released as part of the BRAIN Initiative Cell Network series, dedicated to assembling an exhaustive repository of brain cell types.

Shaojie Ma, a Postdoctoral Associate working in the laboratory of Nenad Sestan, who holds the Harvey and Kate Cushing Professorship in Neuroscience and serves as a Professor in comparative medicine, genetics, and psychiatry at the Yale School of Medicine, co-authored the study as the first author.