Description
Cullins play an essential role in the protein degradation process via the 26S proteasome. These scaffolding proteins are essential components of the ubiquitin ligase which brings a substrate together with ubiquitin. In this study, we have identified homologs of Cullin-3, -4, and -5 in the genome of the planarian Schmidtea mediterranea. We have described expression patterns for these genes as well as the phenotypes exhibited by the animals after RNA interference (RNAi). We have also identified the presence of DDB1, which is an essential part of the Cullin-4 scaffold, its expression pattern and phenotypes resulting from its perturbation. Disruption of proper gene function of Cullin3 through RNAi resulted in a reduction of regeneration. Interference of the proper function of Cullin 4 and DDB1 resulted in a more severe phenotype including death. Our study shows that these genes play essential roles in the maintenance and regeneration of planarians. Defects in the development of the mammalian cerebral cortex lead to several neurological and psychiatric diseases; yet we know little about the mechanisms that regulate cortical development and lead to disease. One disease which results in a neurological phenotype is a multisystem, neonatal lethal condition, designated as the endocrine-cerebroosteodysplasia (ECO) syndrome. This condition is the result of a mutation in Intestinal Cell Kinase (ICK) which has been shown to regulate cell cycle progression. ICK is part of a small family of serine threonine kinases that share similarities with both MAP kinases and cyclin dependent kinases; MOK is also part of this family. MOK is highly homologous to ICK and shares a 41-43% identity between catalytic domains. Since both kinases are similar in their structure it is possible that they will share a similar functional role. MOK is expressed in the intestinal crypt and brain and has been shown to play a role in the stem cell niche of the intestinal crypt by leading to an arrest of proliferation and inducing differentiation. In order to identify the molecular pathways that regulate cortical development, we have been studying whether MOK regulates self-renewal, differentiation and migration of neural stem cells in the developing cerebral cortex. We have disrupted endogenous gene function by means of shRNA expression and observed a phenotype which manifested as a decrease in electroporated cells reaching the cortical plate. This phenotype was partially rescued using the human version of MOK. While it appears that this kinase may be playing a role in cortical development, more experiments need to be performed to determine the exact role of MOK in these processes.
