The three-dimensional structure of human organs is essential for function, and understanding how organs are constructed from cells is a huge challenge in biology. One important mechanism involves bending sheets of connected cells. A new type of cell sheet bending called 'basal constriction' has recently been discovered in the brain. This project will uncover genes necessary for basal constriction, using the zebrafish. The zebrafish is an excellent model as the embryo is transparent, allowing microscopic imaging of single cells in the living animal. It is hypothesized that a cellular communication system called the 'Wnt-PCP pathway' is essential for basal constriction. The function(s) of genes in this pathway, including one called focal adhesion kinase will be examined. A hypothesis that membrane around part of the cell is removed by a process called 'endocytosis' to constrict the cell and bend the cell sheet will be tested. This project is groundbreaking, since it brings together the disciplines of tissue structural engineering and molecular biology. Basal constriction occurs in many organs, and knowledge obtained from these studies will be pertinent for understanding organ formation and regeneration.
The broader impacts of the project include trainee mentoring, training, and communicating with the public. Mentorship will include middle school students through Boston Science Club for Girls. Undergraduates will participate in this research, while graduate students and postdoctoral researchers will be trained as effective supervisors. The PI has a special interest in encouraging young women to consider a research career, and will mentor and lead discussions for this group. The PI also has a strong interest in mentoring postdoctoral researchers, and set up an annual review process for Whitehead/MIT postdocs. Lectures on the importance of scientific inquiry and the excitement of research will be offered to lay audiences in various venues.
