CAREER: Investigating robustness during organogenesis with undergraduate researchers

About This Grant

Organ formation occurs in individuals with different genetic variations and under different environmental conditions. While extreme genetic and environmental variations such as severe loss-of-function mutations or exposure to toxic chemicals can lead to birth defects, not all loss-of-function mutations or chemical exposures result in birth defects. This is because biological recovery and robustness mechanisms enable organ formation to occur normally over a surprisingly large range of genetic and environmental changes. This study seeks to identify these recovery and robustness mechanisms, specifically focusing on the heart. Knowledge of these mechanisms will help researchers understand how birth defects arise and may also lead to remedies. This study is enabled by utilizing the zebrafish embryonic model system which provide the unique benefits of high conservation to human development while being an intact genetically manipulable organism in which inter-tissue communication and organ development in individual embryos and can be observed in real-time. By intertwining this research with undergraduate education (courses and research experiences), this study will increase undergraduate participation in research while also elucidating fundamental principles of organ formation. Heart development, similar to the development of other organs, occurs in uniform stereotypical stages. The initial stage of heart formation, called cardiac fusion, involves bilaterally specified myocardial cells which collectively move towards the midline and merge together to form a single population. In zebrafish the process of cardiac fusion is followed by the processes of cardiac jogging, lumen formation, looping and chamber formation. Intriguingly, heart development can recover from defects in the initial stage of cardiac fusion to eventually form a functional heart. In elucidating the tissue-level mechanisms that facilitate this recovery, this study is focused on determining if there is plasticity in the timing and coordination of the different developmental stages that underlie heart formation? Additionally, this work will expand undergraduate participation in research by creating new undergraduate research-centered courses and an intensive summer research program in which undergraduate students not only learn about recovery and robustness mechanisms but also participate in research to identify new molecules and environmental factors that influence the processes robustness and recovery. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.