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Research Focus and Representative Scientific Discoveries

Life is thought to have originated from RNA. According to von Baer’s law, the zygote and early embryo most closely resemble the primordial state of life, making them natural hotspots for RNA-centered regulation. Indeed, most maternal factors deposited in oocytes are either RNAs themselves or RNA-binding proteins. Using the zebrafish early embryo as an entry-point and integrating mammalian models, our group uncovers novel RNA regulatory mechanisms and dissects their roles in cell differentiation and innate immunity. In parallel, we develop and refine genetic tools for efficient maternal-factor studies.

1. New Mechanisms Underlying Early Embryonic Development

Identified the maternal organizer Rbm24a protein in zebrafish germ granules, showed that it forms a complex with Buc to recruit germ-plasm RNAs and govern primordial germ-cell differentiation (The EMBO Journal, 2025). Demonstrated that zygotically expressed Rbm24a is a new component of the cytoplasmic polyadenylation (CPA) complex. Specifically enriched in lens fiber cells, it boosts mRNA stability and translation, preventing cataract formation (PNAS, 2020). Showed that the Wnt scaffold protein Dishevelled (Dvl) is dispensable for maternal Wnt/β-catenin activation and dorsal organizer induction, challenging the long-held view that maternal Dvl/Wnt ligands are “dorsal determinants” (PLoS Genetics, 2018). Elucidated the role of the newly identified maternal transcript vrtn in dorsoventral axis formation (Development, 2017). Found that the maternal protein Lurap1 binds Dvl to repress the Wnt/PCP pathway, thereby controlling cell polarity and directed migration (Nature Communications, 2017).

2. A Cross-Species Conserved Double-Stranded RNA Sensor

Double-stranded RNA (dsRNA) is a universal pathogen-associated molecular pattern and a hallmark of viral replication. While dsRNA sensors switch during differentiation, a stem-cell-specific sensor had not been identified. Using zebrafish and mouse embryos as well as mouse embryonic stem cells, we discovered that PRKRA homodimers act as a stem-cell-specific, evolutionarily conserved dsRNA receptor. We further resolved how PRKRA hijacks the eIF2 complex to impose global translational repression (Molecular Cell, 2025). Inspired by this work, we further elucidated that dsRNA by-products generated during in vitro transcription of mRNA are key contributors to the toxic effects observed in gene overexpression experiments. Moreover, we demonstrated that incorporating N1-methyl-pseudouridine (m¹Ψ) modifications enables these dsRNA by-products to evade surveillance by the dsRNA sensor Prkra. As a result, m¹Ψ modification prevents stress responses induced by in vitro–transcribed mRNA injections and markedly enhances translation efficiency (Nucleic Acids Research, 2025).

3. Rapid Genetic Strategies for Maternal Mutant Generation

• Pioneered a mosaic approach to obtain maternal-zygotic double mutants of dvl2 and dvl3a (PLoS Genetics, 2018). Established a fast oocyte-specific conditional knockout technique that yields maternal mutants within a single generation and efficiently removes large genomic segments (Science Advances, 2021). These methods circumvent embryonic lethality of zygotic mutants (The EMBO Journal, 2025) and greatly accelerate functional studies of maternal factors (JoVE, 2025).

We welcome students and researchers with backgrounds in developmental biology, biochemistry and molecular biology, or bioinformatics to join our group in uncovering the mysteries of embryonic development.

Positions for permanent staff and postdoctoral researchers are currently open.

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Ming Shao

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