Temporal control of vulval precursor cell fate patterning in Caenorhabditis elegans

Development of a multicellular organism requires precise coordination of temporal and spatial cues to ensure that developmental events occur at the correct time and place. C. elegans vulval development offers a convenient experimental system for investigating the temporal and spatial regulation of multiple developmental decisions in response to different patterning signals. In this thesis, I present my studies on the temporal control of Vulval Precursor Cell (VPC) fate patterning through analyses of VPC development defects in heterochronic mutants. I show that loss of the miRNA lin-4 inhibits LIN-12/Notch activity through persistence of LIN-14, but not LIN-28 or HBL-1. Persistent lin-14 blocks LIN-12 activity without interfering with the key events of LIN-12/Notch signal transduction, and lin-14 activity in the second larval stage is sufficient to prevent premature LIN-12 activation. I also present evidence that persistent lin-14 activity impedes extension of the VPC apical domains, and that ectopic Wnt signaling prevents the daughters of uninduced VPCs from fusing with the major hypodermal syncytium in lin-4 null mutants. Finally, through characterization of heterochronic mutants that exhibit precocious or delayed vulval induction, I provide clues to possible mechanisms underlying the temporal control of vulval induction.