Developmental Biology, Genetics
The Johns Hopkins University
Dr. Seydoux is also the Huntington Sheldon Professor in Medical Discovery in the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine.
Embryonic Polarity and the Soma-Germline Dichotomy
Among the first steps in the complex journey from embryo to adult is the decision as to which cells will become somatic cells, destined to form the body, and which will become germline cells, destined to form the reproductive organs. The developing embryo must commit to both of these cellular types with precision and accuracy, but little is known about the molecular differences between the two.
For Geraldine Seydoux, the roundworm C. elegans provides the vehicle for understanding this process. Specifically, she focuses on how a key developmental process called polarization establishes distinct anterior and posterior regions in a single-celled embryo. The anterior region will subsequently develop into the embryo's somatic domains and the posterior into germline domains.
Seydoux and her team have discovered that the C. elegans egg is polarized by a structure brought in with the sperm at fertilization. This structure, called a microtubule-organizing center (MTOC), triggers the relocalization of several proteins in the egg's cortex into distinct anterior and posterior domains. Interactions among the asymmetrically localized proteins are then what maintains the egg's polarity.
Delving into the mechanisms cells use to establish their identity, she has found that germ cells depend on the global inhibition of messenger RNA synthesis to maintain their fate. Unable to make their own mRNAs, germ cells depend on mRNAs inherited from the egg and the precise regulation of mRNA translation to express germline proteins. In contrast, somatic cells synthesize their own mRNAs and degrade most egg mRNAs.
Seydoux plans to further explore how the MTOC signal divides the egg into anterior and posterior domains and how the regulatory proteins in the egg control that polarization. Although her work focuses on the roundworm, many of the mechanisms she studies are evolutionarily conserved in other organisms, and may well yield insights into development of mammals and other animals.