Title: Nuclear organogenesis requires nuclear surface area regulation through nucleo-cytoplasmic trafficking
Abstract: Throughout development, nuclei must be assembled following every cell division to establish a functional organelle from compact chromatin. During nuclear organogenesis, chromatin expands to establish a nucleus of a given size, which is dictated by cell size. Determining how nuclear expansion is regulated during nuclear organogenesis is particularly significant in the context of certain cancers in which scaling relationships between cell and nuclear sizes are not maintained. In Xenopus egg extract droplets of specified volumes, we determine that nuclear surface area does not scale with cytoplasmic volume, whereas nuclear volume does. Looking to explain differential nuclear scaling relationships, we developed a simple mechano-chemical mathematical model. In simulating biological perturbations in silico, our model predicted crucial roles for nucleo-cytoplasmic trafficking in regulating nuclear expansion and in regulating the recruitment of a nuclear surface area factor, which we propose is LMNB1. Inhibiting nuclear export increased nuclear expansion rates and reduced the amount of LMNB1 being recruited to assembling nuclei in mammalian cells, supporting our model’s predictions. Targeting nuclear export in the Drosophila syncytial embryo, we show that nuclear expansion rates are also increased in this biological context, consistent with our model. Additionally, we demonstrate a role for nuclear export in regulating transcription activation timing and dynamics following nuclear organogenesis, suggesting that regulating nuclear assembly is crucial for downstream nuclear function. Taken together, we propose a simple model through which nuclear organogenesis is achieved in several organisms and demonstrate a role for nuclear export in regulating nuclear expansion and nuclear surface area. Subsequent work will be aimed at identifying the molecular requirements for nuclear expansion and nuclear lamina assembly.
Speaker link: http://labs.bio.unc.edu/Maddox/
Host: Jun Allard