A nervous system enhancer underwent accelerated evolution in primates and shows heterochrony during brain development in transgenic mice

Abstract

A nervous system enhancer underwent accelerated evolution in primates and shows heterochrony during brain development in transgenic mice.Stopiello, J.M., López-Leal R., Rubinstein, M and Franchini, L.F.The lineage leading to humans underwent an expansion in cortical brain size which is, at least in part, responsible for the particular cognitive abilities of primates and particularly of humans. Aiming to identify the genetic elements that underlie brain evolution in primates, we found a 400 bp region that shows signatures of acceleration in the primate lineage and that we have named AANC. In contrast, the gene that is regulated by AANC shows a very high conservation from insects to mammals and shows no sign of acceleration in the primate lineage. This gene is key for neurogenesis during the development of the central nervous system (CNS).Using a transgenic reporter assay in mouse and zebrafish, we tested the ability of the murine AANC to act as an enhancer in the CNS during development. We found that mouse AANC drives, in a very specific manner, reporter expression to the ventricular zone of the mouse neocortex during neurogenesis. In order to understand the biological meaning of the DNA changes that occurred in AANC in primates, we conducted transgenic reporter assays in mouse using the human AANC. We conclude that human AANC can expand the spatial and temporal expression of the reporter activity in mouse compared to murine AANC. This works shows that AANC is a strong brain developmental enhancer which expanded its temporal and spatial expression pattern in primates and help us to understand genetic and molecular mechanisms that could be important in primate brain evolution.