Cellular and Molecular Neurobiology
Author: Gonzalo Nicolas Dominguez Paredes | Email: gonzalodp316@gmail.com
Gonzalo Nicolas Dominguez Paredes1°, Leandro Caporale1°, Lucia Florencia Franchini1°
1° Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
Our work aims to uncover the links between genetic changes and the evolution of the human brain. We hypothesize that the acquisition of new expression patterns in brain developmental genes in the human lineage was critical for the neuroanatomical evolution of our brain. We focus on non-coding regions of the human genome showing accelerated evolution (Human Accelerated Regions: HARs) compared to other vertebrates. The FOXP2 gene, known for its role in speech development, is of particular interest. Using transgenic zebrafish and mice, we demonstrated that two HARs within the FOXP2 locus, HACNS750 and HACNS169, act as transcriptional enhancers during brain development. Both HARs exhibit gain of function when comparing human and chimpanzee sequences. We hypothesize that these HARs regulate FOXP2 expression via interaction with its promoters, and that sequence changes in the human lineage led to new expression patterns in FOXP2-controlled genes, impacting brain development. To further investigate, we are generating genetically modified mice using CRISPR/Cas9. In this poster, we present our HACNS750 knock-out (KO) mice and our strategy to generate HACNS169 KO mice, as well as the creation of knock-in (KI) mice, where the murine versions will be replaced by the human orthologs.