Female Meiosis

Contact: Keith Jones

Research in the Keith Jones Lab

Meiosis is the name given to the two cell divisions germ cells go through, following DNA replication, in order to produce haploid gametes. Our research focuses on female meiosis where we use imaging based techniques to explore this process in real-time. We are very much interested in how the two meiotic divisions are controlled at a molecular level. Our approach is to over-express and visualise gene products by tagging them with a toolkit of Fluorescent Proteins (Cyan; Cerulean; Yellow, Green; Venus; and Red Fluorescent Proteins) and knock them out using antisense morpholinos. It is important to develop dynamic methods to study essentially a dynamic process.  Meiosis is important to study because it is a unique type of cell division that needs to be executed with precision in order to create a viable embryo. However meiotic errors do occur, especially as women get older, and such errors are the leading cause of early pregnancy loss and also are responsible for Down's Syndrome.

Research Highlights: The mammalian oocyte spends most of its life arrested at prophase of the first meiotic division and in 2006 we found that APCcdh1 activity was necessary in order to achieve this arrest (Reis et al., Nature Cell Biology, 2006). We extended these observations to show that APCcdh1 also functioned in prometaphase to prevent aneuploidy in maturing oocytes (Reis et al., Nature Cell Biology, 2007).  In the first meiotic division chromosome homologues are separated, a unique cell division, and also in 2006 we found that during this division separase is needed to inhibit MPF activity (Gorr et al., Nature Cell Biology, 2006). Following exit from the first meiotic division the egg re-arrests at metaphase of the second meiotic division until sperm break this arrest with a cytosolic calcium signal. Re-arrest at metaphase of the second meiotic division requires the APC inhibitor Emi2 (Madgwick et al., Journal of Cell Biology, 2006). At fertilization the sister chromatids are separated. Another unequal cell division occurs, and the second polar body is extruded. The fertilized oocyte completes meiosis and forms a zygote.

See our recent papers in Nature Cell Biology

Complete list of K.Jones Laboratory Publications: Keith is on the Editorial Board of the following Journals:
Biology of Reproduction	Developmental Biology	Reproduction

Current Laboratory Members:-

Publications from the Keith Jones Lab

• Jones KT (2010) Cohesin and Cdk1: an anaphase barricade. Nature Cell Biology, 12: 106-8.
• Holt JE et al (2010) Spatial regulation of APCCdh1 induced cyclin B1 degradation maintains G2 arrest in mouse oocytes. Development,  137: 1297-1304.
• Chang HY et al  (2009) Calmodulin-dependent protein kinase gamma3(?3) mediates the cell cycle resumption of metaphase II eggs in mouse. Development, 136: 4077-4081.
• Jones KT (2008) Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age. Human Reproduction Update 14:143-58. I
• Reis A et al (2007) Prometaphase APCcdh1 activity prevents non-disjunction in mammalian oocytes. Nature Cell Biology 9:1192-8. [NCB website]   
• Levasseur M et al (2007) A novel mechanism controls the Ca2+ oscillations triggered by activation of ascidian eggs and has an absolute requirement for CDK1 activity. Journal of Cell Science 120:1763-71
• Madgwick S et al (2006) Mouse Emi2 establishes a metaphase II spindle by re-stabilizing cyclin B1 during interkinesis. Journal of Cell Biology 174:791-801
• Reis A et al (2006) The CRY box: a second APCcdh1 -dependent degron in mammalian cdc20. EMBO Reports 7:1040-5
• Gorr IH et al (2006) Essential CDK1-inhibitory role for separase during meiosis I in vertebrate eggs. Nature Cell Biology 8:1035-7 [NCB News & Views] [NCB Website]   
• Reis A et al (2006) APCcdh1 activity in mouse oocytes prevents entry into the first meiotic division. Nature Cell Biology 8:539-40 [NCB website]

Journals: Last updated June 2010

Fertilization

First Meiosis