Kui Liu

Professor
Molecular biology

Phone: +46 (0)31-786 6585
E-mail: kui.liu@cmb.gu.se
Visiting address: Medicinaregatan 9C

Mechanisms Regulating Female Germ Cell Development and Pre-implantation Embryonic Development in Mammals

We are interested in studying mechanisms, especially signaling molecules, controlling the development of female germ cells and pre-implantation embryos in mammals.

Overview of published work:

(I) During the past decade, we have identified a few molecules that control the survival, the activation, and the demise of primordial follicles. Our work suggested that the phosphatidylinositol 3-kinase (PI3K) signaling pathway, together with other related pathways, such as the TSC/mTORC1 and p27/Cdk systems, are fundamental players in manipulating the development and aging of the mammalian ovary. We are also trying to dissect mechanisms regulating the formation of primordial follicles in mammals.

Selected references:

• Zhang H, Zheng W, Shen Y, Adhikari D, Ueno H and Liu K. Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries. Proceedings of the National Academy of Sciences. 2012. In Press.
• Reddy P, Zheng W, Liu K. Mechanisms maintaining the dormancy and survival of mammalian primordial follicles. Review. Trends Endocrinol Metab. 21(2):96-103. 2010.
• Adhikari D, Zheng WZ, Hämäläinen T., Huhtaniemi I., and Liu K. Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Human Molecular Genetics. 19(3):397-410. 2010.
• Adhikari D and Liu K. Molecular mechanisms underlying the activation of mammalian primordial follicles. Review. Endocrine Reviews. 30(5):438-64. 2009.
• Reddy P., Adhikari D, Zheng WZ, Hämäläinen T., Ogawa W., Noda T., Volarevic S., Huhtaniemi I., and Liu K. PDK1 signaling in oocytes controls reproductive aging and lifespan by manipulating the survival of primordial follicles. Human Molecular Genetics. 18(15):2813-24. 2009.
• Reddy P., Liu L., Adhikari D., Jagarlamudi K., Rajareddy S., Shen Y., Du C., Tang W., Hämäläinen T., Peng S.L., Lan Z.J., Cooney A.J., Huhtaniemi I. and Liu K. Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science. 319, 611-613, 2008.
• Rajareddy S., Reddy P., Du C., Jagarlamudi K., Tang W.L., Shen Y., Berthet C., Peng. S.L., Kaldis P. and Liu K. p27kip1 (Cdkn1b) controls ovarian development by suppressing follicle endowment and activation, and promoting follicle atresia in mice. Molecular Endocrinology. 21, 2189-2202. 2007.

(II) In addition, we have recently identified the PI3K pathway as an indispensable maternal signaling that controls the pre-implantation embryonic development. If the PI3K signaling is blocked in oocytes (but not in sperms), the derived embryos are found to be arrested at the 2-cell stage, with defected embryonic genome activation (EGA) that is probably a cause, or related to the cell cycle arrest.

References:

• Zheng W., Gorre N., Shen Y., Noda T., Ogawa W., Lundin E., and Liu K. Maternal PI3K signaling is crucial for embryonic genome activation and preimplantation embryogenesis. EMBO Reports. 2010. 11(11):890-5.
• Zheng W, Liu K. The emerging role of maternal phosphatidylinositol 3 kinase (PI3K) signaling in manipulating mammalian preimplantation embryogenesis. Minireview. Cell Cycle. 2011. 10(2):178-9

We would like to further study the molecular mechanisms underlying the development of mammalian ovaries and embryos, and provide functional evidence showing the involvement of certain molecules and signals.

The research team currently consists of the following people: principal investigator Kui Liu, postdoc researcher Hua Zhang, Ph.D. students Wenjing Zheng, Gorre Nagaraju, Sanjiv Risal, Zhiyi Zhao, and Deepak Adhikari, and project student Annelieke Strijbosch. Most of the time we also have 1-2 project/master students. We are constantly looking for highly qualified and motivated students and postdocs. For more information, please contact Kui Liu at kui.liu@cmb.gu.se.