Abstracts - Society for Developmental Biology

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decisions: How many times should each neuroblast and each daughter cell divide? To address these questions we are
studying several lineages. We find that the first proliferation decision, Type I, is under the control of the homeodomain
protein Prospero. In contrast, the second decision, Type 0, is under control of Notch. Neither Pros nor Notch is involved in
the neuroblast cell cycle exit. Global analysis of proliferation control in the CNS reveal that these mechanisms are broadly
used. To address the pathway by which Notch controls the daughter proliferation switch we have finally analyzed a number
of HES genes, as well as the expression of several key G1 cell cycle genes.
Program/Abstract # 86
A global genomic survey of genes that mediate PAR-4/LKB1-dependent germline stem cell quiescence in C. elegans
Chaouni, Rita; Roy, Richard, McGill University, Montreal, Canada
LKB1 is aserine/threonine protein kinase that is implicated in the rare, autosomal dominant disease Peutz-Jeghers
syndrome (PJS). In addition to its causative role in PJS, it is also often mutated in sporadic cancers, suggesting that LKB1
acts as a bona fide tumor suppressor. Understanding how LKB1 exerts its tumor suppression is therefore of prime
significance. LKB1 affects numerous developmental processes including cell growth and cell polarity. When
Caenorhabditis elegans larvae encounter harsh environmental conditions, they can alter their developmental course and
enter dauer diapause, where the germline stem cells are consequently rendered quiescent. Previous work has revealed that
PAR-4, the homologue of LKB1, is required for this arrest and PAR-4 deficient dauer larvae display hyperplasia of the
germline at this stage. Although LKB1 is known to activate AMPK (aak-1/aak-2 in C. elegans), it is unlikely that AMPK is
the sole mediator of germline stem cell quiescence downstream of LKB1/PAR-4. To better understand the tumor
suppressor function of PAR-4, we continued to dissect its role in regulating cellular quiescence in developmentally arrested
larvae. A genome-wide RNA interference-based screen was performed to identify suppressors of PAR-4-mediated
germline hyperplasia. We have identified several genes whose loss of function was found to rescue the germline
hyperplasia observed in par-4 dauer larvae. Future endeavors entail the characterization of key candidates, many of which
impinge on the actin cytoskeleton and its regulation. Further understanding of the function of these genes will provide
additional insight as to how LKB1/PAR-4 blocks tumorous growth by regulating cell cycle quiescence.
Program/Abstract # 87
LKB1 dependent and independent roles in the establishment and maintenance of germline stem cell quiescence in
C. elegans
Kadekar, Pratik; Navidzadeh, Nathan; Wendland, Emily; Roy, Richard, McGill Univesity, Montreal, Canada
C. elegans execute a diapause like state called ‘dauer’ when they encounter harsh environmental conditions. This stage is
associated with global developmental arrest that facilitates their survival in unfavorable growth conditions. Curiously the
signals that normally drive germline stem cell (GSC) proliferation are present and active in dauers, therefore we became
interested in dissecting the pathways that mediate quiescence in the GSC during this diapause stage. It was previously
shown that the C. elegans orthologs of LKB1, STRAD, AMPK and PTEN are required in establishing quiescence in the
dauer germline. LKB1 acts through AMPK in order to regulate the cell cycle arrest in GSCs. Interestedly, LKB1
knockdown in AMPK null mutants show an additive effect suggesting anAMPK-independent role for LKB1 in the
regulation of this quiescence. To identify novel LKB1 targets that may be involved in process, a genome-wide RNAi
screen was performed in order to isolate genes that caused germline hyperplasia upon their knockdown during the dauer
stage. The screen allowed us to identify 39 candidate genes and 7 of them are involved in regulating cell polarity and
cytoskeletal regulation. LKB1 regulates early embryonic polarity and therefore may affect cell polarity in the GSC
independently of AMPK to affect quiescence.We have categorized the candidates from this screen to show which
candidates function dependently and independently of both LKB1 and AMPK. Our candidates fall into at least two classes:
1) Those that affect early phases of quiescence (establishment) i.e. par-3. 2) Those that show a phenotype in late dauer
(maintenance) i.e. cdc-42 and rho-1. How these effectors regulate GSC quiescence is currently under investigation.
Program/Abstract # 88
Centrosome elimination during C. elegans development
Lu, Yu; Roy, Richard, McGill University, Montreal, Canada
Centriole duplication is coupled with cell division to ensure that the centriole is duplicated only once per cell cycle.
However, this coupling can be altered in specific developmental contexts, although how this uncoupling occurs remains
misunderstood. In C.elegans, the larval intestinal cell will undergo one nuclear division followed by four endocycles. We
use this model to understand how the centriole is coupled to the cell cycle and the mechanisms though which they can be
uncoupled during the alternative cell cycles that occur throughout development. By monitoring the levels of SPD-2, a
protein critical for centriole duplication in C. elegans, we found that the centriole duplicates normally at the L1 nuclear