Vertebrate evolution took a crucial turn about 320 million years ago, when early tetrapods transitioned from water to land, eventually giving rise to three major clades: the reptiles, the birds (an evolutionary offshoot of reptiles), and the mammals. Due to their common ancestry, the brains of all tetrapods share a similar basal architecture established early in evolution. However, how variations in this common architecture contributed to clade-specific attributes remained a mystery for a long time.
Now, a team of researchers from the Max Plank Institute for Brain Research in Frankfurt, Germany, has attempted to clarify these issues by generating a molecular atlas of the brain of the Australian bearded dragon (Pogona vitticeps) and comparing it with that of mice.
The widespread belief was that mammalian brains consist of ancient reptilian brains supplemented with new mammalian features. However, the study revealed that both mammalian and reptilian brains developed their own clade-specific neuron types and circuits, from a common ancestral set.
“Neurons are the most diverse cell types in the body. Their evolutionary diversification reflects alterations in the developmental processes that produce them and may drive changes in the neural circuits they belong to,” explained study senior author Gilles Laurent, the director at the Max Planck Institute.
“For example, distinct brain areas do not work in isolation, suggesting that the evolution of interconnected regions, such as the thalamus and cerebral cortex, might in some way be correlated. Also, a brain area in reptiles and mammals that derived from a common ancestral structure might have evolved in such a way that it remains ancestral in one clade today, while it is “modern” in the other. Conversely, it could be that both clades now contain a mix of common (ancient) and specific (novel) neuron types. These are the sorts of questions that our experiments tried to address.”
By using a cellular transcriptomic approach that employs single-cell RNA sequencing to detect large fractions of the RNA molecules – or “transcriptomes” – present in single cells, the scientists mapped and compared the brains of P. vitticeps with that of mice.
“We profiled over 280,000 cells from the brain of Pogona and identified 233 distinct types of neurons,” said study first author David Hain, a graduate student in Professor Laurent’s lab. “Computational integration of our data with mouse data revealed that these neurons can be grouped transcriptomically in common families, that probably represent ancestral neuron types.”
Further analyses revealed that neurons in the thalamus can be grouped into two transcriptomic and anatomical domains, defined by their connectivity to other regions of the brain. These connected regions have different fates in mammals and reptiles, one of them being highly divergent. Comparing the thalamic transcriptomes of the two domains revealed that transcriptomic divergence matched that of the target regions.
“This suggests that neuronal transcriptomic identity somewhat reflects, at least in part, the long-range connectivity of a region to its targets. Since we do not have the brains of ancient vertebrates, reconstructing the evolution of the brain over the past half billion years will require connecting together very complex molecular, developmental, anatomical and functional data in a way that is self-consistent. We live in very exciting times, because this is becoming possible,” Professor Laurent concluded.
The study is published in the journal Science.