Oocyte symmetry breaking and polarity by the COC
Oocyte polarity and embryonic development
The Balbiani body (Bb) is a large mRNP granule that is universal to all oocytes from insects to humans. In mammals, the Bb is associated with primordial follicle formation by an unclear mechanism. In most vertebrates, such as fish and frogs, it is crucial for embryonic development. The Bb polarizes the early oocyte along the animal-vegetal (AV) axis, and localizes factors to the vegetal cortex of the oocyte that later pattern the embryo and specify the germline cell fate (Top panel in the figure below). When a Bb fails to form, oocytes and embryos remain radially symmetric and soon die (bottom panel).
Despite its conservation and developmental consequences, Bb formation remained poorly understood for 170 years. How it forms, and what determines its cellular position were unknown. We have identified the symmetry breaking events that initiate the formation of the Bb, at the very onset of oocyte differentiation. We found that at these early stages, oocyte polarization and Bb formation are mechanistically coupled with a polarized nuclear configuration that functions in meiosis (panel A in the figure below). In this configuration, called the chromosomal bouquet, all telomeres are tethered to the nuclear envelope and clustered to one pole of the nucleus, while the free looping chromosomes face the other side. The bouquet is a universal phenomenon that is required for chromosomal pairing toward meiotic recombination.
Bouquet formation requires microtubules that are based from the centrosome. We found that at these stage, Bb precursor transition from a radial distribution, to become polarized around the centrosome, in a microtubule dependent manner (panel B). This for the first time shows a coupling between the meiotic program and the patterning of the oocyte, and we proposed that the bouquet centrosome functions as a Centrosome Organizing Center (COC) (panel C) that coordinates these two processes in oocyte differentiation. The COC is likely conserved from insects to mammals.
In this project we are asking two major questions:
1. How does the COC mechanistically recruit Bb granules to polarize the oocyte?
2. What is the contribution of the physical coordination between the nuclear and cytoplasmic compartments in
We are taking a genetic approach by generating CRISPR/Cas9 mutants to study COC mechanisms and have developed an unbiased stage specific proteomics method to find novel factors and regulators of specific steps in COC functions.