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Control of Cell Division and Quiescence During "C. Elegans" Developement

出版	McGill University, 2008
URL	http://books.google.com.hk/books?id=no0ZuAEACAAJ&hl=&source=gbs_api

註釋The development of the nematode C. elegans is invariant allowing investigators to use genetic analysis in this model system to identify components of many critical developmental pathways. The Roy laboratory uses this strategy to identify genes that control cell division throughout the course of development. My work focusses on the intestinal lineage due to their typical cell division pattern. Using genetic analysis, I have characterized the role of genes that affect the transition from mitosis to karyokinesis and finally endoreplication that occurs in the intestinal cells post-embryonically during the first larval stage. Five mutants that were isolated are grouped into classes that have more (rr33 and rr45) or less (rr42, rr43 and rr44) intestinal nuclei than wild-type. I cloned both mutants with more intestinal nuclei (rr33 and rr45) to show that they encode lin-35, the homologue of the Retinoblastoma gene and a highly conserved gene referred to as nol-10 respectively. I showed that lin-35 interacts with RNAi pathway components to properly repress genes required for this transition. I also found that met-2, the homologue of the Suv39h methyl transferase as well as the heterochromatin protein-like hpl-1 and hpl-2 are required to maintain the repression of these loci. Moreover, during my characterization of the typical cell cycle arrest observed during the dauer stage, I found that the Notch ligand lag-2 is specifically expressed in 6 Inter Labial neurons 2 (IL2) at the onset and throughout the dauer stage. I demonstrated that this expression pattern reflects the requirement of the canonical Notch pathway to properly maintain the dauer stage and specific expression of the Notch receptor glp-1 in a subset of neurons is able to rescue the defect in dauer maintenance in glp-1 mutants. Therefore, the Notch pathway is not required for neuronal cell fate specification since there is no cell division at this stage but rather serves a novel function that may in.