D-007 | STUDY OF THE TRANSCRIPTIONAL REGULATION OF THE FOXP2 GENE IN THE HUMAN LINEAGE FROM AN EVOLUTIONARY APPROACH

Cellular and Molecular Neurobiology
Author: Gonzalo Nicolas Dominguez Paredes | Email: gonzalodp316@gmail.com

Gonzalo Nicolas Dominguez Paredes^1°, Leandro Caporale^1°, Lucia Florencia Franchini^1°

^1° Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)

Our research investigates genetic changes related to the evolution of the human brain. We hypothesize that new expression patterns in brain developmental genes were key to neuroanatomical evolution in humans. We focus on non-coding regions of the genome, particularly Human Accelerated Regions (HARs), which have evolved rapidly compared to other vertebrates. Loci near genes like NPAS3, RBFOX1, and FOXP2 are of interest due to their role in brain development. FOXP2, essential for speech development, has been widely studied in human evolution. We identified two HARs within the FOXP2 locus, HACNS750 and HACNS169, as transcriptional enhancers active during brain development. Reporter assays in zebrafish and mice showed that these HARs exhibit gain of function when comparing human and chimpanzee sequences. We propose that these HARs regulate FOXP2 expression via promoter interactions and that human-specific changes led to new expression patterns in FOXP2-regulated genes, impacting brain development. To explore this further, we are generating CRISPR/Cas9-modified mice. This poster presents our HACNS750 knock-out (KO) mice and our strategy for creating HACNS169KO mice, as well as knock-in (KI) mice where the murine versions of these HARs are replaced with their human orthologs.