Cellular and Molecular Neurobiology
Author: Ignacio Leone | Email: firstname.lastname@example.org
Ignacio Leone 1°, Lucía Florencia Franchini 1°
1° Instituto de Investigaciones en Ingeniería Genética y Biología Molecular – Consejo Nacional de Investigaciones Científicas y Técnicas (INGEBI-CONICET)
NPAS3 (Neuronal PAS Domain Protein 3) is a transcription factor largely expressed in the developing brain, and its deficiency in mammals has been correlated with neurophysiological pathology such as epilepsy. To understand the evolution of its transcriptional regulation and expression patterns across history, our team previously designed biocomputational algorithms to detect accelerated genomic regions in mammals: regions that exhibit prolonged conservation in the phylogenetic tree yet in certain branches accumulate nucleotide changes faster than the neutral evolution rate. Among 24,007 mammalian accelerated regions (MARs) we found, 3,476 are non-coding (ncMARs) potentially involved in vertebrate phenotypic innovation. Notably, NPAS3 possesses up to 30 ncMARs, suggesting its relevance in mammalian brain evolution. In this study we will aim to characterise NPAS3-ncMARs as enhancers via transgenic zebrafish assays, shedding light on their transcriptional role. To discern mammalian-specific functional shifts, we will contrast enhancer activity between mammalian and non-mammalian sequences. Upon identifying expression differences in NPAS3-ncMARs, we’ll generate genetically modified mouse models, unveiling evolution’s impact on NPAS3 expression in vivo. Comparing NPAS3 expression in diverse vertebrates will confirm how regulatory region changes have influenced its expression, contributing to novel morphological traits.