EvoBrainShark · Studying sharks to unravel the developmental and cellular mechanisms that shaped the emergence and evolution of the vertebrate brain.

Our view of vertebrate brain evolution is mainly informed by data in mammals. Lacking from this view are cartilaginous fish, that emerged around 450 million years ago with two synergistic innovations: the jaw and predatory behavior. By studying shark embryos, we noted striking similarities with mammals in developmental programs, including the presence of Basal Progenitors (BPs) and Cajal-Retzius cells (CRs), transitory cell types essential for the massive expansion and structural complexity of the mammalian neocortex. The evolutionary origins of BPs and CRs are generally considered as innovations in mammals or amniotes. However, their presence and strong conservation in sharks suggest a much earlier emergence in vertebrate history. We hypothesize that the jawless to jawed vertebrate transition, because it expanded predation, range of food options and habitats, also promoted a substantial expansion and increased complexity of the brain, leaving a strong imprint in developmental programs that are particularly well conserved in sharks. In EvoBrainShark, I propose to reassess the sequence of events that led to the formation and diversification of the jawed vertebrate brain. My team will leverage our expertise in the shark embryo to: 1) investigate the evolution of vertebrate-specic brain developmental programs; 2) predict and validate gene regulatory networks operating on every diversification step; 3) investigate the evolutionary trajectories and roles of BPs and CRs; and 4) leverage functional tools in the shark model to test phenotypic impact of targeted developmental mechanisms. We will combine single-cell and spatial multiomics, bioinformatics, cross-species comparisons, wet-lab developmental biology, and gene editing tools. This project will reveal mechanisms of neural diversification, foster new tools for the emerging shark research community and fundamentally reshape our knowledge of vertebrate brain evolution.