Cells rely upon intra- and extra-cellular signals to choose between various pathways of growth or differentiation. In sexually-reproducing organisms, germline cells must cease mitotic growth and enter meiosis to produce gametes; but the signals triggering growth arrest and entry into meiosis remain poorly understood. In yeast, cells must be starved for nutrients and actively respiring to begin meiosis; but little is known about how cells sense their respiration status and integrate this information with other signals to initiate and complete meiosis. While the nutritional requirements for meiosis are likely specific to yeast, the respiration requirement could be conserved in higher organisms. ? ? OBJECTIVES: The goals of this work are to identify and characterize the respiration-dependent stages of meiosis, and to elucidate how cells sense and respond to respiration in order to initiate meiosis.
SPECIFIC AIMS : 1) To identify respiration-dependent stages of meiosis, 2) to identify factors needed for transmitting the respiration signal to the nucleus, and 3) to investigate the role of RIM101 in transmitting the respiration signal. ? ? STUDY DESIGN: Respiration-dependent stages of meiosis will be identified by inactivating respiration at various times and observing the effects on IME1 expression (a marker of meiosis initiation) and speculation. Any meiotic arrests caused by lack of respiration will be characterized with respect to the cell cycle arrest point and the status of DNA recombination and spore formation. Factors necessary for transmitting the respiration signal will be identified by screening for high-copy and second-site suppressors of the meiotic defects in respiration-deficient strains, and by screening sporulation-defective mutants (identified in the lab) for their ability to express IME1 during meiosis. Finally, the role of the IME1 transcription factor RIM101 in responding to the respiration signal will be analyzed, and the mechanisms of its differential expression in respiring and non-respiring cells will be elucidated. ? ?
Cells in all organisms face the choice between clonal proliferation and other developmental pathways; for sexual reproduction, some cells must cease growth and generate gametes. The inability to cease growth and enter different developmental states can have profound consequences ranging from incorrect limb development in a fetus to cancer in adults. The inability to make gametes occurs as women age, and a correlation between poorly-functioning mitochondria and infertility due to a failure to produce egg cells has been noted. This work will define how cells choose between growth and gametogenesis. ? ? ?
| Jambhekar, Ashwini; Amon, Angelika (2008) Control of meiosis by respiration. Curr Biol 18:969-75 |
