Dissertations, Theses, and Capstone Projects

Date of Degree


Document Type


Degree Name





Alicia Melendez Ph.D


Daniel Weinstein Ph.D

Committee Members

Daniel Weinstein Ph.D

Cathy Savage-Dunn Ph.D

Ana Maria Cuervo, M.D., Ph.D

Iva Greenwald Ph.D

Subject Categories

Biology | Cell and Developmental Biology | Genetics


Autophagy, germ cells, C. elegans, BEC-1, Beclin 1, proliferation


Autophagy is an evolutionary conserved process involved in the cellular adaptation to stress and basal levels of autophagy are crucial for cellular metabolism and homeostasis. Cellular recycling by autophagy is characterized by the formation of distinctive double-membrane vesicles (autophagosomes) that engulf unnecessary cytoplasmic components, such as organelles and long-lived proteins. Failure to remove protein aggregates and/or damaged organelles, via autophagy, has been implicated in various medical conditions such as liver disease, neurodegenerative diseases and cancer. Autophagy may suppress or promote cellular proliferation in tumors, depending on the type and metabolic state of the cell, where autophagy is generally believed to mediate these functions cell-autonomously. Here we evaluate the role of BEC-1 and autophagy gene function in cell proliferation, using the C. elegans germ line as an in vivo model. BEC-1 is the C. elegans ortholog of human BECN1/Beclin 1, an essential autophagy regulator and tumor suppressor protein. We show that basal levels of autophagy are required for germline proliferation and that autophagy genes are necessary for the timely progression of the cell cycle. Interestingly, we noticed that autophagy genes may regulate cell proliferation via several pathways. We show that BEC-1/BECN1 acts independently of the GLP-1/Notch or DAF-7/TFG-β pathways, but interacts with components of DAF-2/IIR signaling pathway, to potentiate germline proliferation during development. Moreover, BEC-1/BECN1 requires DAF-18/PTEN but not DAF-16/FOXO for this function and can both promote and inhibit germ cell proliferation depending on the genetic mutant background. Furthermore, ATG-18 and ATG-16.2 also act independently of the GLP-1/Notch and DAF-7/TFG-beta pathways, however it seems that they interact with the canonical of DAF-2/IIR signaling pathway and require DAF-18/PTEN and DAF-16/FOXO for their function. Interestingly, ATG-7 functions together with the DAF-7/TFG-β and independently of the GLP-1/Notch and DAF-2/IIR signaling pathways to promote stem/progenitor cell proliferation. Thus, we conclude that autophagy regulates cellular proliferation in a multifaceted way, probably through interactions with components of at least two non-mutually exclusive signaling pathways: DAF-2/IIR and DAF-7/TFG-β. Our findings indicate that autophagy and BEC-1/BECN1 functions non-cell autonomously, to control germ line proliferation by facilitating cell cycle progression and that BEC-1/BECN1 is probably important for the G2 to M phase transition. Given the evolutionary conservation of autophagy genes from C. elegans to humans, understanding the molecular mechanisms by which autophagy genes modulate the proliferation and/or maintenance of the stem progenitor cell population in vivo may lead to novel autophagy based chemotherapeutic approaches in the future.