171 | Transcriptional analysis of the splicing factor RBFOX1 and the transcription factor NPAS3 and their role in human brain evolution


Author: Tomás Gusmerini | Email: tomas@gusme.com

Tomás Gusmerini , Lara Berasain , Marcelo Rubinstein , Florencia Lucía Franchini

1° INGEBI-CONICET (Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres”)

Morphological and functional evolution may result from changes in regulatory elements. We suggest studying differences in these regions tied to core genes in the developing brain to understand the human brain’s genetic basis for morphological and cognitive differences. Key developmental genes, RBFOX1 and NPAS3, experienced accelerated non-coding evolution in humans, accumulating numerous Human Accelerated Regions (HARs), many acting as transcriptional enhancers in transgenic tests. However, these enhancers are just a portion of potential gene-regulating non-coding regions. To explore 7400 potential enhancers in NPAS3 and RBFOX1 loci marked by ENCODE, we’ll employ a massive parallel reporter assay (MPRA) on human neural stem cells for enhancer scoring. This technique helps compare genetic variations between humans and other lineages and assess variant effects in regulatory regions. MPRA results will be validated by creating transgenic zebrafish lines expressing eGFP for selected elements. Genetically engineered mice will also test RBFOX1-HARs, evaluating effects on RBFOX1 expression, brain development, epilepsy, and neurodevelopmental disorders.