Science has published two studies, led by an Ikerbasque researcher at the Achucarro Basque Center for Neuroscience and UPV/EHU, uncovering their unique evolutionary path.

The pallium is the brain region where the neocortex develops in mammals, playing a key role in cognitive and complex functions that distinguish humans from other species. Traditionally, the pallium has been considered a structurally comparable region across mammals, birds, and reptiles, differing primarily in complexity.

It was previously believed that this region contained similar types of neurons and equivalent circuits for sensory and cognitive processing. Earlier studies identified shared excitatory and inhibitory neurons, along with general connectivity patterns, suggesting a common evolutionary trajectory among these vertebrates.

However, two new studies have shown that while the pallium serves analogous functions across these groups, its developmental mechanisms and the molecular identity of its neurons have significantly diverged over the course of evolution.

The first study, conducted by Eneritz Rueda-Alaña and Fernando García-Moreno at Achucarro, with the support of a multidisciplinary team of collaborators from the Basque research centers CICbioGUNE and BCAM, the Madrid-based CNIC, the University of Murcia, Krembil (Canada), and Stockholm University, shows that while birds and mammals have developed circuits with similar functions, the way these circuits form during embryonic development is radically different.

“Their neurons are born in different locations and developmental times in each species,” explains Dr. García-Moreno, head of the Brain Development and Evolution laboratory, “indicating that they are not comparable neurons derived from a common ancestor.”

Using spatial transcriptomics and mathematical modeling, the researchers found that the neurons responsible for sensory processing in birds and mammals are formed using different sets of genes.

“The genetic tools they use to establish their cellular identity vary from species to species, each exhibiting new and unique cell types.” This all indicates that these structures and circuits are not homologous, but rather the result of convergent evolution, meaning that “they have independently developed these essential neural circuits through different evolutionary paths.”

Comparing the Avian, Mammalian, and Reptilian Brain

The second study further explores these differences. Conducted at Heidelberg University (Germany) and co-directed by Bastienne Zaremba, Henrik Kaessmann, and Fernando García-Moreno, it provides a detailed cell type atlas of the avian brain and compares it with those of mammals and reptiles.

“We were able to describe the hundreds of genes that each type of neuron uses in these brains, cell by cell, and compare them with bioinformatics tools.”

The results show that birds have retained most inhibitory neurons present in all other vertebrates for hundreds of millions of years. However, their excitatory neurons, responsible for transmitting information in the pallium, have evolved in a unique way. Only a few neuronal types in the avian brain were identified with genetic profiles similar to those found in mammals, such as the claustrum and the hippocampus, suggesting that some neurons are very ancient and shared across species.

“However, most excitatory neurons have evolved in new and different ways in each species,” details Dr. García-Moreno.

The studies, published in Science, used advanced techniques in spatial transcriptomics, developmental neurobiology, single-cell analysis, and mathematical modeling to trace the evolution of brain circuits in birds, mammals, and reptiles.

Rewriting the Evolutionary History of the Brain

“Our studies show that evolution has found multiple solutions for building complex brains,” explains Dr. García-Moreno. “Birds have developed sophisticated neural circuits through their own mechanisms, without following the same path as mammals. This changes how we understand brain evolution.”

These findings highlight the evolutionary flexibility of brain development, demonstrating that advanced cognitive functions can emerge through vastly different genetic and cellular pathways.

The importance of studying brain evolution

“Our brain makes us human, but it also binds us to other animal species through a shared evolutionary history,” explains Dr. García-Moreno.

The discovery that birds and mammals have developed neural circuits independently has major implications for comparative neuroscience. Understanding the different genetic programs that give rise to specific neuronal types could open new avenues for research in neurodevelopment.

Dr. García-Moreno advocates for this type of fundamental research: “Only by understanding how the brain forms, both in its embryonic development and in its evolutionary history, can we truly grasp how it functions.”

References: “Evolutionary convergence of sensory circuits in the pallium of amniotes” by Eneritz Rueda-Alaña, Rodrigo Senovilla-Ganzo, Marco Grillo, Enrique Vázquez, Sergio Marco-Salas, Tatiana Gallego-Flores, Aitor Ordeñana-Manso, Artemis Ftara, Laura Escobar, Alberto Benguría, Ana Quintas, Ana Dopazo, Miriam Rábano, María dM Vivanco, Ana María Aransay, Daniel Garrigos, Ángel Toval, José Luis Ferrán, Mats Nilsson, Juan Manuel Encinas-Pérez, Maurizio De Pittà and Fernando García-Moreno, 14 February 2025, Science.
DOI: 10.1126/science.adp3411

“Developmental origins and evolution of pallial cell types and structures in birds” by Bastienne Zaremba, Amir Fallahshahroudi, Céline Schneider, Julia Schmidt, Ioannis Sarropoulos, Evgeny Leushkin, Bianka Berki, Enya Van Poucke, Per Jensen, Rodrigo Senovilla-Ganzo, Francisca Hervas-Sotomayor, Nils Trost, Francesco Lamanna, Mari Sepp, Fernando García-Moreno and Henrik Kaessmann, 14 February 2025, Science.
DOI: 10.1126/science.adp5182