Genetic analysis of nuclear bodies: from nondeterministic chaos to deterministic order

The eukaryotic nucleus is a congested place, and macromolecular crowding is thought to have an important role in increasing the relative concentrations of nuclear proteins, thereby accelerating the rates of biochemical reactions. Crowding is also thought to provide the environment needed for formation of nuclear bodies/subcompartments, such as the Cajal body (CB) and the histone locus body (HLB), via self-organization. In this chapter, we contrast the theories of stochastic self-organization and hierarchical self-organization in their application to nuclear body assembly, using CBs and HLBs as paradigms. Genetic ablation studies in Drosophila on components of CBs and HLBs have revealed an order to the assembly of these structures that is suggestive of a hierarchical model of self-organization. These studies also show that functions attributed to the nuclear bodies are largely unaffected in their absence, reinforcing an emerging theme in the field that the purpose of these subdomains may be to enhance the efficiency and specificity of reactions.