Grant: Project Grant

Mammalian development is an incredibly complex yet self-regulated process driven by molecular interactions encoded in the genome. It begins with a single fertilized egg that divides to give rise to specialized cells. As development unfolds, cells activate specific genes in response to internal and external signals, directing their functions. Cells also communicate with one another through signaling, coordinating the formation of tissues and organs in a highly organized manner. Understanding this process is essential, as disruptions in developmental programs can lead to congenital diseases in humans. Over the past 30 years, scientists have discovered a distinct class of small, non-protein-coding genes known as microRNAs, which play a crucial role in this process. To date, approximately 1,900 microRNAs have been identified in humans and 1,200 in mice. Each microRNA can regulate thousands of target genes, primarily by suppressing or fine-tuning their activity. Many microRNAs are now recognized as essential for mammalian development, and mutations in these genes have been linked to congenital disorders. Despite their importance, there is currently no method to comprehensively map how microRNAs influence body formation. To address this, our team has developed a genome engineering technology capable of capturing the activity of many microRNAs simultaneously. In this project, we will refine and expand this technology to create the first spatial atlas of microRNA activity throughout the entire developing mouse body. This resource will provide fundamental insights into how mammals develop and how disruptions in microRNA activity contribute to disease. Ultimately, our findings will enhance our understanding of developmental disorders and inform new therapeutic strategies in human health.