Neurons are polarized cells with specialized processes known as dendrites that receive environmental stimuli and transduce that input to the cell body, or soma. Dendrites are important in generating action potentials for cell-to-cell communication and, in the case of sensory neurons, for sensing the environment. Despite the important role that dendrites play, the molecular mechanisms that regulate dendrite development, or morphogenesis, are poorly understood. Recent research indicates that dendrite morphogenesis is regulated by the localized control of messenger RNA (mRNA) in dendrites. mRNA localization and translational regulation is often mediated by RNA-binding proteins (RBPs), which recognize and bind to specific mRNAs. It is thought that regulating protein translation in dendrites, which are located far from the nucleus where mRNAs originate, is a faster and more efficient way to regulate dendrite morphogenesis than changing gene expression. A recent study has found that the RBP gene brat regulates dendrite morphogenesis in Drosophila. To determine if brat function is conserved, we studied the role of ncl-1, a C. elegans homolog of brat, in dendrite morphogenesis. Dendrite morphology in wild type and ncl-1 mutants was compared using a fluorescent marker that is expressed in the PVD mechanosensory neurons in C. elegans. We find that ncl-1 null mutant PVDs have fewer dendritic branches than wild type throughout development. Consistent with a role in PVD dendritic development, we find that ncl-1 is expressed in most neurons during development, likely including the PVD. Since NCL-1 may be involved in regulating mRNAs in dendrites we wanted to see where within neurons the NCL-1 protein is localized. We find that NCL-1 is localized to both axons and dendrites, but was excluded from the nucleus. Together, these results suggest that NCL-1 plays a conserved role as an RBP that regulates mRNAs important for dendrite elaboration and future studies will be aimed at learning which mRNAs NCL-1 binds and how it regulates them.
Neurons have highly asymmetric cellular morphologies and polarized cellular functions that are necessary for establishing neural circuitry and for proper functioning of the nervous system. Specialized processes, called dendrites, are used by neurons for reception of stimuli, while axons function in the transmission of signals. In neurons, mRNA localization and translational repression are used to change the protein composition of various regions of the cell, allowing for distinct axonal and dendritic morphologies and environments that are equipped for their various cellular tasks. A significant portion of the eukaryotic genome encodes for RNA-binding proteins (RBPs), which play important roles in localizing and translationally regulating RNAs. Since studies have shown that a large number of mRNAs are localized within dendrites, this suggests that the RBPs contribute broadly to neuronal development and function by localizing and regulating mRNAs. Based on a previous screen of RBP-encoding genes that affect dendrite morphogenesis in dendritic arborization neurons (da neurons) in Drosophila that identified 89 genes (Olesnicky, Killian, and Gavis; in preparation), I extended this screen to determine if any of these evolutionarily conserved RBP genes are important for dendrite morphogenesis in C. elegans PVD neurons as well. A significant decrease in dendritic arborization was found in dcr-1 mutants and preliminary results suggest that sup-26 and mtr-4 mutants may have decreased 3rd and 4th order dendritic branching. In addition, several other candidate genes are currently being investigated. Thus far, the results suggest that DCR-1/Dicer, an RBP involved in the microRNA pathway, SUP-26/Alan Shepard, an RBP implicated in translational control of mRNAs, and MTR-4/L(2)35Df, a component of the eukaryotic RNA exosome play an evolutionarily conserved role in dendrite development in flies and worms.