Same destination, different journeys: how do different animals evolve similar brain structures?

In Chapter 13 of "Principles of Neurobiology," the evolution of the nervous system is examined from various angles, including the expansion of the mammalian neocortex (13.20). About 350 million years ago, during the early Permian period, the evolution of the vertebrate nervous system saw a significant event with the transition of early tetrapod (meaning four-limbed vertebrate) from water to land. The clade of tetrapods that moved to land is called amniotes, which excludes amphibians. Amniotes further split into sauropsids (reptiles and birds) and synapsids (mammals). Despite hundreds of millions of years of evolution, the six-layered mammalian neocortex and the dorsal ventricular ridge (DVR) found in sauropsids share many similarities in gene expression, connectivity, and function. It has long been thought that the two structures have the same origin.

However, recent advances in single-cell RNA sequencing have provided new insights into these brain structures. Previous analyses of turtle and lizard DVRs revealed that their excitatory neurons have distinct gene expression profiles compared to excitatory neurons in the mammalian neocortex. This raises the alternative hypothesis that the two structures have separate origins and that the similarities could be the result of convergent evolution. In a recent study by Woych et al., the authors found potential molecular evidence supporting the hypothesis by single-cell transcriptomic analysis of an amphibian species, salamander Pleurodeles waltl. The authors reasoned that if the reptile DVR and mammalian neocortex evolved separately, the cells in these two regions may trace back to different brain regions in the common preamniote ancestor, whose cellular transcriptome signatures may still be present in the existing amphibian species.

The authors performed single cell RNA sequencing on the brain of P. waltl and obtained 36,115 cells, including 29,294 neurons. Cell type clustering based on gene expression differences revealed 47 excitatory and 67 inhibitory neuron types. They then mapped the spatial distribution of these cells using in situ hybridization with cell type-specific marker genes. The spatial mapping showed that different cell types were distributed in adjacent longitudinal stripes along the pallium (dorsal telencephalon, or the anterior-most part of the brain) ridge running the entire length of the telencephalon. Sequencing of the developing brain, which contains the progenitor cell population, captured the developmental trajectories of pallium cell types. Different pallium cell types not only differ in their gene expression at the adult stage but also develop from different lineages. Using this new zonal information, the authors compared the cell types in P. waltl to those in reptiles (Australian bearded dragon Pogona vitticeps and red-eared slider turtle Trachemys scripta) and mammals (mouse). The cross-species analysis revealed that part of the reptile DVR has molecular similarities to cells in the amphibian ventral pallium. In contrast, the mammal neocortex does not share molecular similarities with the amphibian pallium. There are cells in the mammal hippocampus, entorhinal cortex, and subiculum that map to the amphibian dorsal pallium. Hippocampus, subiculum, and entorhinal cortex belong to allocortex, which has 3 to 4 layers rather than 6 layers. These findings support the hypothesis that the similarities of mammalian neocortex and sauropsid DVR are the result of convergent evolution rather than sharing a common ancestor (homologous). The sauropsid DVR may have originated from the amphibian pallium.

Finally, the authors studied the circuit similarity by tracing the projection pattern. They observed connectivity similar between amphibian dorsal pallium and mammalian hippocampus-subiculum- entorhinal cortex, as well as between amphibian ventral pallium and reptile DVR.

It remains unclear where mammalian neocortex originated from—did it come from a yet-to-be identified region in amphibian pallium, or did it originate de novo? This remains to be explored.

Figure 1: Connectivity of the P. waltl pallium. Top: schematic representation of amphibian, reptile, and mammalian brains. Colors indicate molecular and connectivity similarities of neuron types across species. Cross-hatching denotes areas with cell-type innovations. MP/medial cortex, hippocampus, and mammalian subiculum are not shown in the drawing. Bottom: phylogenetic tree. DCtx, dorsal cortex; Ent, entorhinal cortex; LCtx, lateral cortex; Pir, piriform cortex; Sub, subiculum.

Reference:

Woych, J. et al. Cell-type profiling in salamanders identifies innovations in vertebrate forebrain evolution. Science https://doi.org/10.1126/science.abp9186 (2022)