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Lei LI, Ph. D.

Molecular Basis of Early Embryonic Development


Co-workers: Xiaoxin Zhang, Wenbo Liu, Zheng Gao, Yang Yu, Yi Xiao, Haixia Ma, Xukun Lu, Jinglin Zhang, Yusheng Liu, Huaixiao Ma, Dandan Qin, Xiaoxiao Wang, Yuxuan Lin, Xiaoqing Nie, Xiaoqing Wang

· LI Group website

 

  By using genetics, embryo culture and ES cells as the model systems, our researches focus on molecular and cellular basis of early embryonic development and gametogenesis.

  Research directions:

  1)Cell lineage specification of early embryonic development: Early embryonic cells are totipotent, progressively differentiate into pluripotent, and then commit to three germ layer cells. Recently, we have established an efficient in vitro culture (IVC) system to support mammalian blastocysts grow beyond gastrulation. We have also derived a mammalian formative pluripotent stem cells (fPSCs), which is poised for gastrulation. By using these systems, we are investigating genetic and epigenetic controls of early cell lineage commitment during embryonic development.

  2) Maternal control of vertebrate early embryogenesis: Prior zygotic genome activation, early embryogenesis is entirely controlled by maternal effect genes. Recently, we have identified oocyte-embryo specific expressed SCMC that is essential for mammalian early embryogenesis. Currently we focus on the molecular mechanisms of subcortical maternal complex (SCMC). In addition, we investigate maternal DNA damage repair and maternal RNA degradation during vertebrate maternal-to-zygotic transition.

  3) Molecular mechanism of mammalian gametogenesis: We found some alternative pre-mRNA splicing factors specifically expresses and play important role in mouse gametogenesis. Currently, we investigate how these factors regulate mouse gametogenesis by using mouse genetic and RNA-sequence approaches.



Localization (A) and a model (B) of the SCMC (Li et al., Dev. Cell, 2008).



The SCMC regulates the symmetric division through F-actin in mouse zygote (Yu et al., Nat. Commun., 2014).



Formative pluripotent stem cells (fPSCs), (Wang et al., Cell Res, 2021).

 

 

Plain English:
We are interesting in cell lineage specification of early embryonic development and also interesting in the genes specifically expressed in germ cell that play important roles during early embryonic development and gametogenesis. Our searches will contribute to the clinic application of stem cells, human reproductive disorders and contraception.

 

Selected publications:

  1. Ma H, Zhai J, Wan H, Jiang X, Wang X, Wang L, Xiang Y, He X, Zhao Z, Zhao B, Zheng P*, Li L*, Wang H*. In vitro culture of cynomolgus monkey embryos beyond early gastrulation. Science. 2019 Oct 31. pii: eaax7890. doi: 10.1126/science. aax7890. [Epub ahead of print].
  2. Qin D, Gao Z, Xiao Y, Zhang X, Ma H, Yu X, Nie X, Fan N, Wang X, OuYang Y, Sun QY, Yi Z, Li L*. The subcortical maternal complex protein Nlrp4f is involved in cytoplasmic lattice formation and organelle distribution. Development. 2019 Oct 18; 146 (20). pii: dev183616. doi: 10.1242/dev.183616.
  3. Lu X, Zhao Z, Wang X, Zhang X, Zhai Y, Deng W, Yi Z*, Li L*. Whole-transcriptome splicing profiling of E7.5 mouse primary germ layers reveals frequent usage of alternative promoter during early embryogenesis. Biology Open. 2018, Mar; 7(3). bio032508.
  4. Gao Z, Zhang X, Yu X, Qin D, Yu Y, Liu W, Xiang Y, Xiao Y, Lu X, Yi Z, Li L*. Zbed3 participates in the subcortical maternal complex and regulates the distribution of organelles. Journal of Molecular Cell Biology. 2018 Feb; 10(1): 74-88.
  5. Yu Y, Wang X, Zhang X, Zhai Y, Lu X, Ma H, Zhu K, Zhao T, Jiao J, Zhao Z*, Li L*. ERK inhibition promotes neuroectodermal precursor commitment by blocking self-renewal and primitive streak formation of the epiblast. Stem Cell Research & Therapy. 2018 Jan; 9(1): 2. doi: 10.1186/s13287-017 -0750-8.
  6. Lu X, Gao Z, Qin D, Li L*. A maternal functional module in the mammalian oocyte-to-embryo transition.Trends in Molecular Medicine. 2017 Nov; 23 (11) 1014–1023.
  7. Liu W Wang F, Xu Q, Shi J, Zhang X, Lu X, Gao Z, Ma H, Zhao Z, Duan E, Gao F, Gao S*, Yi Z*, Li L*. BCAS2 is involved in alternative mRNA splicing in spermatogonia and the transition to meiosis. Nature Communications. 2017 Jan 27; 8:14182.
  8. Xiao Y, Ma H, Wan P, Qin D, Zhang X, Xiang Y, Wang X, Liu W, Chen J*, Yi Z*, and Li L*. Trp-Asp (WD) repeat domain 1 is Essential for Mouse Peri-implantation Development and Regulates Cofilin Phosphorylation. Journal of Biological Chemistry. 2017 Jan 27; 292(4):1438-1448.
  9. Liu Y, Lu X, Shi J, Yu X, Zhang X, Zhu K, Yi Z, Duan E, Li L*.BTG4 is a key regulator for maternal mRNA clearance during mouse early embryogenesis.Journal of Molecular Cell Biology 2016 Aug; 8(4):366-8. 
  10. Ma H, Lin Y, Zhao Z, Lu X, Yu Y, Zhang X, Wang Q*, Li L*.MicroRNA-127 Promotes Mesendoderm Differentiation of Mouse Embryonic Stem Cells by Targeting Left-right Determination Factor 2.Journal of Biological Chemistry 2016 Jun 3; 291(23):12126-35.
  11. Xu Q, Wang F, Xiang Y, Zhang X, Zhao Z, Gao Z, Liu W, Lu X, Liu Y, Yu X, Wang H,  Huang J, Yi Z, Gao S*, Li L*. Maternal BCAS2 protects genomic integrity in mouse early embryonic development. Development. 2015 Nov 15; 142(22):3943-53.
  12. Zhao Z-A, Yu Y, Ma H-X, Wang X, Lu X, Zhai Y , Zhang X-X, Wang H, Li L*. The roles of ERAS during cell lineage specification of mouse early embryonic development. Open Biology. 2015 Aug; 5(8).
  13. Zhu K, Yan L, Zhang X, Lu X, Wang T, Yan J, Liu X, Qiao J*, Li L*. Identification of a human subcortical maternal complex. Molecular Human Reproduction. 2015 Apr; 21(4): 320-9.
  14. Yu X, Yi Z, Gao Z, Qin D, Zhai Y, Chen X, Ou-Yang Y, Wang Z, Zheng P, Zhu M, Wang H, Sun QY, Dean J*, Li L*. The subcortical maternal complex controls symmetric division of mouse zygotes by regulating F-actin dynamics. Nature Communications. 2014 Sep 11; 5:4887.
  15. Li L*, Lu X and Dean J*. The maternal to zygotic transition in mammals. Molecular Aspects of Medicine. 2013 Oct; 34(5): 919-38.
  16. Li L*, Zheng P and Dean J*. Maternal Control of Early Mouse Development. Development. 2010 Mar; 137(6): 859-70.
  17. Li L*, Baibakov B and Dean J. A Subcortical Maternal Complex Essential for Pre-implantation Mouse Embryogenesis. Developmental Cell. 2008 Sep; 15(3): 416-25.