A new study changes the scientific paradigm on the evolutionary origins of the brain in vertebrates

An international team has published in the journal PLOS Biology, an article which alters the classic model of the brain formation process in vertebrates and its biological evolution. The new study, conducted with animal models (amphioxus, zebrafish and mice), is led by the experts Jordi García-Fernàndez, from the Institute of Biomedicine of the University of Barcelona (IBUB); José Luis Ferran and Luis Puelles, from the University of Murcia (UMU), and Manuel Irimia, from the Center for Genomic Regulation (CRG).

According to one of the most accepted models, the brain in vertebrates is created out of a neural tube, distinguished in the forebrain (prosencephalon), midbrain (mesencephalon) and hindbrain (rhombencephalon). This traditional view would not be the proper one after the results now revealed by the evolutionary developmental biology (evo-devo). According to the new study, the brain in vertebrates would have developed out of two regions (fore and hind) instead of three, which was believed in the prosomeric or segmentary model.

Genoarchitecture: new views on the nervous system

The experts created a detailed molecular map of the regions in which the amphioxus brain is divided. This is a reference animal model in genomics and one of the most basic representatives of the branch the chordate division.

According to Beatriz Albuixech-Crespo (UB-IBUB), post-doctoral researcher and first signer of the study, “genoarchitecture is the point of experimental reference for the new work in order to define the regionalization process of the amphioxi neural tube and to compare it to the one in the nervous system of vertebrates. Therefore, we created a molecular map of the gene expression pattern in the amphioxi with gene orthologs –created out of a common ancestor through speciation process- which take part in the development and regionalization of the nervous system in vertebrates”.

“In the study, we described this molecular map –which contains the largest number of markers so far- with the divisions that occur in the neural plate of the cephalochordate”, says Albuixech-Crespo. “With this positional information, we looked for topological equivalences in a homologue structure, in particular, the neural plate in vertebrates”, continued.

The study aims to understand what the brain in amphioxus is like. According to José Luis Ferran (UMU), “comparing the areas shown in the brain of modern vertebrates to the one in amphioxus, we study the possible causes for this multiplication and the creation of such a complex structure during our evolution as a species”.

HyPTh and DiMes: a change in the paradigms on the origins and evolution of the brain

Both the amphioxus brain and the one in vertebrates are divided into two main regions (fore and hind), said the authors. In the case of the amphioxus, everything suggests that the fore region was divided in two main areas with internal subdivisions, while in vertebrates, the equivalent regions are topologically preserved but they undergo a higher degree of regionalization. The authors note that the hindbrain of the amphioxus is highly regionalized, like in vertebrates’ hindbrains.

In the forebrain, the comparative analysis between the neural plate in vertebrates and cephalochordates has also enabled the definition of HyPTh, a new region that would equal to the region where hypothalamus, telencephalon and prethalamus appear in vertebrates. The article also notes that the role of the diencephalon as a barrier between the forebrain and midbrain would not be consistent under the criteria of developmental biology (evo-devo).

“The diencephalon does not make up the frontier of the forebrain and therefore, it does not represent a developmental unit. In addition, thalamus, pretectum and mesencephalon, are more related and build an evolutionary unit. Therefore, we should make a redefinition of the forebrain including the forebrain and midbrain from the classical model. This forebrain would be internally divided by separating the subunits that would create the diencephalon”, says Beatriz Albuixech-Crespo.

Researchers did not find brain cortex in amphioxi nor an exclusive region causing the creation of the vertebrates’ midbrain. However, there is a common area in the forebrain –known as DiMes- from which the midbrain and other important structures of the classic forebrain would derive.

“In vertebrates –says Albuixech-Crespo – the region with the thalamus, pretectum and mesencephalon is delimited between the secondary organizers ZLI and IsO. In the amphioxi, the region corresponding to the thalamus, pretectum and msesncephalon (DiMes) is not subdivided but it maintains genetic barriers that define the position of secondary organizers in vertebrates”.

In vertebrates, three important brain regions –which are essential to process sensory information- came out of the topologically equivalent area to the amphioxus’ DiMes. According to the experts, the hypothesis that these regions were created and gave rise to other brain areas independently is wrong. According to Manuel Irimia (CRG), with a doctorate degree from the UB (Faculty of Biology), “in evolution, the three classic brain regions in vertebrates (thalamus, pretectum and mesencephalon) appeared as a result of the molecular signaling centers that cause the spread and partition of the DiMes-like portion”.

The long evolutionary story of the brain in vertebrates
More than 500 million years ago, an evolutionary process began, originating the building foreground of the central system, shared by all vertebrates. Studying gene networks that gave identity to different brain regions is essential to understand how they evolved and to understand the origins of different pathologies. Under the evo-devo perspective, genoarchitecture becomes a powerful tool to detail the areas in the nervous system and the genes that have been active in each area during the developmental process.

“During these last years, the knowledge brought by the new discipline known as evo-devo has been essential to understand evolutionary processes in animals, including our species, and to identify essential genetic elements involved in different human pathologies (obesity, diabetes, neuropathologies, etc.) This view, which is spreading in areas that are far from the human activity, is essential to understand the functioning and evolution of the ecosystems and the environment” concludes Jordi García-Fernández, from the Department of Genetics, Microbiology and Statistics of the UB and IBUB.