CELL CYCLE DECISIONS IN DEVELOPMENT

 

Most prior work has focused on the G0 quiescent state that is established after cells exit mitosis. However, certain stem cell populations quiesce at the G2 stage of the cell cycle, right after the completion of DNA replication. But despite its emerging prevalence across a wide evolutionary spectrum, the mechanisms that allow for the establishment of G2 quiescence and how cells exit the G2 quiescence state to resume proliferation remain understudied.

During development, one of the most important decisions that cells make is whether to continue proliferate or to enter a state of cell cycle pause known as cell cycle quiescence. Cells enter and exit quiescence in response to developmental cues or nutrient signaling. Failure of cells to quiesce results in tumorogenesis, whereas premature quiescence establishment can lead to developmental arrest.

​​The nascent C. elegans germline presents a unique opportunity to study G2 quiescence in the context of a physiologically regulated tissue. In C. elegans, two germ cell precursors are born during embryogenesis, at about the 100-cell stage, replicate their DNA and then enter a quiescent G2 state for the remainder of embryogenesis. After hatching, these precursors remain quiescent until the larva gains access to food, after which germ cells enter mitosis and divide.

 

Using a combination of cell biology, proteomics, genetic screens and developmental analyses we are aiming to answer three key questions:

 

1. What mechanisms control entry into G2 quiescence?

2. How does external signaling regulate exit from G2 quiescence?

 

3. How do these signals interface with the cell cycle?

 Pablo Lara-Gonzalez, Taekyung Kim, Arshad Desai. (2017)  Taming the Beast: Control of APC/C Cdc20-Dependent Destruction. Cold Spring Harbor Symposia on Quantitative Biology 82: 111-121

 Pablo Lara-Gonzalez, Mark W Moyle, Jacqueline Budrewicz, Jose Mendoza-Lopez, Karen Oegema, Arshad Desai (2019) The G2-to-M Transition Is Ensured by a Dual Mechanism that Protects Cyclin B from Degradation by Cdc20-Activated APC/C.  Developmental Cell 51: 313-325