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Updated: Sep 6, 2025
In Vivo Calcium Imaging in C. elegans Body Wall Muscles
Published on: October 20, 2019
DDX1 vesicles control calcium-dependent mitochondrial activity in mouse embryos
Yixiong Wang1, Lubna Yasmin1, Lei Li1
1Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, T6G 1Z2, Canada.
Abstract:
The DEAD box protein DDX1, previously associated with 3'-end RNA processing and DNA repair, forms large aggregates in the cytoplasm of early mouse embryos. Ddx1 knockout causes stalling of embryos at the 2-4 cell stages. Here, we identify a DDX1-containing membrane-bound calcium-containing organelle with a nucleic acid core. We show that aggregates of these organelles form ring-like structures in early-stage embryos which we have named Membrane Associated RNA-containing Vesicles. We present evidence that DDX1 is required for the formation of Membrane Associated RNA-containing Vesicles which in turn regulate the spatial distribution of calcium in embryos. We find that Ddx1 knockout in early embryos disrupts calcium distribution, and increases mitochondria membrane potential, mitochondrial activity, and reactive oxygen species. Sequencing analysis of embryos from Ddx1 heterozygote crosses reveals downregulation of a subset of RNAs involved in developmental and mitochondrial processes in the embryos with low Ddx1 RNA. We propose a role for Membrane Associated RNA-containing Vesicles in calcium-controlled mitochondrial functions that are essential for embryonic development.
Insights
The DEAD box protein DDX1 forms novel organelles called Membrane Associated RNA-containing Vesicles essential for early embryonic development. These vesicles regulate calcium distribution, impacting mitochondrial function and preventing developmental arrest.
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Genetics
Background:
- The DEAD box protein DDX1 is known for roles in RNA processing and DNA repair.
- DDX1 aggregates in the cytoplasm of early mouse embryos, and its absence causes developmental arrest.
- The precise function of DDX1 in early embryogenesis remains unclear.
Purpose of the Study:
- To elucidate the function of DDX1 in early mouse embryonic development.
- To characterize the novel DDX1-containing structures observed in early embryos.
- To investigate the role of these structures in calcium regulation and mitochondrial function.
Main Methods:
- Identification and characterization of DDX1-containing organelles using microscopy.
- Analysis of Ddx1 knockout mouse embryos to assess developmental phenotypes.
- Assessment of calcium distribution, mitochondrial membrane potential, and reactive oxygen species levels.
- RNA sequencing analysis of embryos with varying Ddx1 expression levels.
Main Results:
- A novel organelle, the Membrane Associated RNA-containing Vesicle (MARV), containing DDX1 and nucleic acids, was identified.
- DDX1 is essential for MARV formation, which exhibit ring-like structures in early embryos.
- Ddx1 knockout disrupts embryonic calcium distribution, increases mitochondrial activity and ROS, and leads to developmental arrest.
- Downregulation of developmental and mitochondrial RNAs correlates with low Ddx1 RNA levels.
Conclusions:
- DDX1 is crucial for the formation of MARVs, which regulate spatial calcium distribution in early embryos.
- MARVs play a vital role in calcium-controlled mitochondrial functions essential for embryonic development.
- Dysregulation of MARVs and calcium homeostasis contributes to developmental defects observed in Ddx1 knockout embryos.
