Selected publications
Shifts in embryonic oxygen levels cue heterochrony in limb initiation
Meng Zhu, ChangHee Lee, Rinaldo Catta-Preta, Clifford J. Tabin*
Cell, 2026
Mammalian embryos are known to have delayed hindlimb development comparing to the forelimb. This is historically termed as limb heterochrony, which is likely a strategy for for viviparity adaptation. We found that the initiation of limb heterochrony is mediated by the hypoxic environment where embryos grow, and the hypoxic responsive pathways and transcription factors. Together this highlights how environmental factors can instruct the timing of foetus tissue development.
Developmental clock and mechanism of de novo polarization of the mouse embryo
Meng Zhu, Jake Cornwall-Scoones, Peizhe Wang, Charlotte E. Handford, Jie Na,
Matt Thomson, Magdalena Zernicka-Goetz*
Science, 2020
The early days of mammalian embryo development follows intrinsic developmental clock that is not dependent on embryo size or cell-cell contact. This is well reflected on the establishment of cell polarity. In the mouse embryo this happens at the 8-cell stage (E2.5) and in human 8- to 16-cell stage (E4). We deciphered the constitution of this developmental clock as it is triggered by zygotic genome activation and the expression of transcription factors Tfap2c and Tead4. These two factors work with Rho GTPases to establish the apical cell polarity.
Principles of Self-Organization of the Mammalian Embryo
Meng Zhu, Magdalena Zernicka-Goetz*
Cell, 2020
DOI: 10.1016/j.cell.2020.11.003
This review summaries my perspective on how mammalian embryos achieve developmental plasticity through cross-talking mechanics and gene regulatory network establishing lineages
Tead4 and Tfap2c generate bipotency and a bistable switch in totipotent embryos to promote robust lineage diversification
Meng Zhu, Maciej Meglicki, Adiyant Lamba, Peizhe Wang, Christophe Royer, Karen Turner, Muhammad Abdullah Jauhar, Celine Jones, Tim Child, Kevin Coward, Jie Na & Magdalena Zernicka-Goetz *
Nature Structural & Molecular Biology, 2024
The mouse and human embryo gradually loses totipotency before diversifying into the inner cell mass (ICM, future organism) and trophectoderm (TE, future placenta). We found that transcription factors Tfap2c and Tead4 accelerate the loss of totipotency through HIPPO signalling. We propose that the bistable switch established by TFAP2C and TEAD4 is exploited to trigger robust lineage diversification in the developing embryo.
Full list of publications
- Zhu M; In preprints: re-examining the role of oxygen in mammalian embryogenesis. Development 1 April 2026; 153 (7): dev205661. doi: https://doi.org/10.1242/dev.205661
- Lamba A*, Zhu M*, Meglicki M, Czukiewska S, Balasubramaniam L, Hadas R, Weishaupt N, Patel Ekta M, Kavanagh Yu H, Wang R, Jing N, Zernicka-Goetz M┼. Asynchronous mouse embryo polarization leads to heterogeneity in cell fate specification eLife. 2024 13:RP101140
- Zhu, M. and Tabin, C.J┼. The role of timing in the development and evolution of the limb. Frontiers in Cell and Developmental Biology, 2023 11, p.1135519.
*This review summaries of the variation of limb developmental timing during evolution and the variations in hindlimb development in mammals.
- Zhu M*, Shahbazi M*, Martin A*, Zhang C, Sozen B, Borsos M, Mandelbaum RS, Paulson RJ, Mole MA, Esbert M, Titus S, Scott RT, Campbell A, Fishel S, Gradinaru V, Zhao H, Wu K, Chen ZJ┼, Seli E┼, de Los Santos MJ┼, Zernicka Goetz M┼. Human embryo polarization requires PLC signaling to mediate trophectoderm specification. eLife. 2021 Sep 27;10:e65068. doi: 10.7554/eLife.65068.
- Zhu M┼, Zernicka-Goetz M┼. Principles of Self-Organization of the Mammalian Embryo. Cell. 2020 Dec 10;183(6):1467-1478. doi: 10.1016/j.cell.2020.11.003.
- Zhu M, Zernicka-Goetz M┼. Living a Sweet Life: Glucose Instructs Cell Fate in the Mouse Embryo. Dev Cell. 2020 Apr 6;53(1):1-2. doi: 10.1016/j.devcel.2020.03.012.
- Zhu M, Zernicka-Goetz M┼. Building an apical domain in the early mouse embryo: Lessons, challenges and perspectives. Curr Opin Cell Biol. 2020 Feb;62:144-149. doi: 10.1016/j.ceb.2019.11.005. Epub 2019 Dec 21.
- Zhu M, Leung CY, Shahbazi MN, Zernicka-Goetz M┼. Actomyosin polarisation through PLC-PKC triggers symmetry breaking of the mouse embryo. Nature communications. 2017;8(1):921.
- Leung CY*, Zhu M*, Zernicka-Goetz M┼. Polarity in Cell-Fate Acquisition in the Early Mouse Embryo. Curr Top Dev Biol. 2016; 120:203-34.
- Atsuta Y, Lee C, Rodrigues AR, Colle C, Tomizawa RR, Lujan EG, Tschopp P, Galan L, Zhu M, Gorham JM, Vannier JP, Seidman CE, Seidman JG, Ros MA, Pourquié O, Tabin CJ. Direct reprogramming of non-limb fibroblasts to cells with properties of limb progenitors. Dev Cell. 2024 Feb 5;59(3):415-430.e8. PubMed Central PMCID: PMC10932627.
- Shen C*, Lamba A*, Zhu M, Zhang R, Zernicka-Goetz M┼, Yang C┼. Stain-free detection of embryo polarization using deep learning. Sci Rep. 2022 Feb 14;12(1):2404. doi: 10.1038/s41598-022-05990-6.
- Singla S, Iwamoto-Stohl LK, Zhu M, Zernicka-Goetz M┼. Autophagy-mediated apoptosis eliminates aneuploid cells in a mouse model of chromosome mosaicism. Nat Commun. 2020 Jun 11;11(1):2958. doi: 10.1038/s41467-020-16796-3.
- Amadei G, Lau KYC, De Jonghe J, Gantner CW, Sozen B, Chan C, Zhu M, Kyprianou C, Hollfelder F, Zernicka-Goetz M┼. Inducible Stem-Cell-Derived Embryos Capture Mouse Morphogenetic Events In Vitro. Dev Cell. 2021 Feb 8;56(3):366-382.e9. doi: 10.1016/j.devcel.2020.12.004. Epub 2020 Dec 29.
- Sozen B, Jorgensen V, Weatherbee BAT, Chen S, Zhu M, Zernicka-Goetz M┼. Reconstructing aspects of human embryogenesis with pluripotent stem cells. Nat Commun. 2021 Sep 21;12(1):5550. doi: 10.1038/s41467-021-25853-4. PMID: 34548496; PMCID: PMC8455697.
- Hupalowska A, Jedrusik A, Zhu M, Bedford MT, Glover DM, Zernicka-Goetz M┼. Inter-relationships of CARM1 and paraspeckles in regulating pre-implantation mouse embryo development. Cell.2018; 175:1902-1916 e1913.
- Shahbazi MN, Scialdone A, Skorupska N, Weberling A, Recher G, Zhu M, et al. Pluripotent state transitions coordinate morphogenesis in mouse and human embryos. Nature. 2017;552(7684):239-43.
* Equal contribution, ┼Corresponding author