Seminario INCYL 2023/2024: Juan Andrés Moriano Palacios

The definition of molecular and cellular mechanisms contributing to evolutionary
divergences in brain ontogenetic trajectories is essential to formulate hypotheses about the
emergence of our species. Yet the functional dissection of evolutionary modifications at an
appropriate level of granularity remains particularly challenging. Capitalizing on recent single-cell
sequencing efforts and using a combination of computational approaches, we have pursued the
characterization of gene regulatory networks at play during indirect neurogenesis and questioned
whether (semi)discrete gene expression programs emerging from the modular nature of such
regulatory networks evolved under different selective pressures. We have resolved the bifurcating
tree defining apical progenitor differentiation and have characterized waves of gene expression
programs showing lineage-specific activation, including a cholesterol metabolic program under the
control of KLF6 zinc-finger transcription factor as putative master regulator. The interplay of
different signaling pathways under selection in the human lineage also points to the need of new
computational approaches to investigate intercellular communication at single-cell resolution.
Overall, our work contributes to studies on the mechanisms implicated in human-specific features
of neocortical expansion.