CORPORATION OF HAVERFORD COLLEGE, THE

DESCRIPTION (provided by applicant): Few processes in biology hold the same degree of fascination as the transformation of a single fertilized egg into a fully differentiated adult organism. What are the genetic mechanisms that physically build and shape us? How are these mechanisms orchestrated and controlled? How do these mechanisms evolve to build all organisms, in all their variety? The goal of this research is to address these questions using insect embryogenesis. The focus of the research is gastrulation: one of the earliest and most transformative embryo-shaping events. Insects are ideal for these studies due to their diversity, abundance, availability, and because the model organism, Drosophila melanogaster, provides an ideal starting point for this analysis which will then be extended to other related model organisms. In Drosophila, the folded gastrulation gene (fog) has been shown to play an important role in coordinating the cell shape changes that drive internalization of cells during gastrulation. The fog gene was thought to be unique to Drosophila but it feeds into a conserved pathway involving a well known signaling cascade (the Rho GTPase) that ultimately leads to activation of a molecular motor that drives the associated changes in cell shape. This raises interesting questions about the evolutionary origin of the novel fog gene, its mechanism of action, and how it relates to components of this pathway in other organisms. This project therefore combines techniques from genetics, bioinformatics, molecular biology, and embryology to achieve the following aims: 1) To trace the evolutionary origin of the fog gene; and. 2) To further analyze the mechanisms of Drosophila gastrulation and fog function. Parallels also exist between Drosophila gastrulation and vertebrate neural tube formation. This research will therefore contribute to the understanding of these parallels and may eventually provide insight into molecular mechanisms that not only underlie insect gastrulation but also play a role in human neural tube formation and congenital neural tube defects. PUBLIC HEALTH RELEVANCE: This project involves studying the molecular and cellular mechanisms of insect embryonic development to gain insight into a specific type of change in cell shape and how genes controlling this process have altered over the course of evolution. These same changes in cell shape are also used to initiate neural tube formation in vertebrates. Results from this project on insect development may therefore help us better understand the complexities of human neural tube formation and the ways that changes to this process result in the formation of congenital neural tube defects.

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