Priyanshi Borad / Biology / Faculty Mentor: Theodora Koromila
Neurodevelopmental disorders, including Attention Deficit Hyperactivity Disorder (ADHD), are often linked to disruptions in early brain development, where transcription factors (TFs) play critical roles in cell fate determination. Our research uses Drosophila as a model organism to investigate conserved mechanisms of neurogenesis, focusing on two TFs, Odd-paired (Opa) and Ocelliless (Oc), which co-regulate gene expression in early brain regions. We hypothesize that Opa and Oc are key regulators of brain lineage specification during pre-gastrulation, influencing neurodevelopmental outcomes. Preliminary in situ analyses confirmed the expression patterns of target genes and enhancer activity within Opa-Oc co-regulated regions, including ems and toy. Our super-resolution live imaging of the toy gene, a conserved early brain marker, has provided spatial and temporal data on TF activity at the single-cell level, revealing intricate details of gene expression dynamics during the early stages of brain development. Notably, Toy protein shares significant sequence conservation with Pax-6 proteins across animal phyla, reinforcing its role as a marker in early brain precursors. We plan to transgenically modify endogenous loci of Opa/Oc target genes to enable live RNA imaging, allowing for precise detection of gene expression variations. By tracking the localization and interaction of toy and associated TFs, we aim to elucidate the molecular mechanisms underpinning brain development. Additionally, by employing CRISPR/Cas9 we are developing two new transgenic lines: ems.CRISPR and toy.CRISPR to investigate the regulatory elements influencing these genes during critical developmental windows. Using CRISPR/Cas9 and Super resolution live imaging analysis, we propose a developmental model for studying early brain lineage formation. Our findings will focus on understanding the genetic architecture behind brain development and its links to neurodevelopmental disorders like ADHD.
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