The morning of life is shrouded in riddle. While the intricate dynamics of mitosis is well- studied in the so- called physical cells – the cells that have a technical function, like skin and muscle cells – they remain fugitive in the first cells of our bodies, the embryonic cells.  Embryonic mitosis is notoriously delicate to study in invertebrates, as live functional analyses and- imaging of experimental embryos are technically limited, which makes it hard to track cells during embryogenesis. 

still, experimenters from the Cell Division Dynamics Unit at the Okinawa Institute of Science and Technology( OIST) have lately published a paper in Nature Dispatches, together with Professors Toshiya Nishimura from Hokkaido University( preliminarily at Nagoya University), Minoru Tanaka from Nagoya University, Satoshi Ansai from Tohoku University( presently at Kyoto University), and MasatoT.  Kanemaki from the National Institute of Genetics. The study takes the first major way towards answering questions about embryonic mitosis, thanks to a combination of new imaging ways, CRISPR/ Cas9 genome editing technology, a ultramodern protein- knockdown system, and medaka, or Japanese rice fish( Oryzias latipes).  The timelapses that they've produced help answer abecedarian questions about the intricate process of inversely dividing chromosomes during embryonic mitosis, and contemporaneously chart the coming frontier of scientific disquisition.  As Professor Tomomi Kiyomitsu, elderly author of the study, describes the timelapses" they are beautiful, both on their own and because they lay a new foundation for expounding embryonic mitosis. "Central to the riddle of embryonic mitosis is the pivotal step when the chromosomes, which contain all the inheritable information of the cell, are aligned and insulated inversely into son cells.  A crucial player in this process is the mitotic spindle, which is made of microtubules – long protein filaments used forintra-cellular structure and transport – that radiates from contrary poles of the spindle and attaches to the chromosomes in the middle.  The spindle captures duplicated chromosomes duly and segregates them inversely into the son cells during division. There are numerous factors determining spindle conformation, and one of these is the protein Ran- GTP, which plays an essential part in cell division of womanish reproductive cells, which warrant centrosomes – cell organelles responsible for assembling microtubules – but not in small physical cells, which do have centrosomes.  still, it has long been unclear whether Ran- GTP is needed for spindle assembly in invertebrate early embryos, which contain centrosomes but have unique features, like a larger cell size. 

In discrepancy to mammalian early embryos, embryonic cells in fish are transparent and develop synchronously in a livery, single- cell subcaste distance, which makes them significantly easier to track.  The medaka turned out to be particularly well- suited for the experimenters, as these fish tolerate a wide range of temperatures, produce eggs daily, and have a fairly small genome.  Being temperature-tolerant means that the medaka embryonic cells could survive at room temperature, making them particularly suited for long, live timelapse photography.

The fact that medaka produce eggs constantly and have a fairly small genome size makes them good campaigners for CRISPR/ Cas9- intermediated genome editing. With this technology, the experimenters have created genetically modified, or transgenic, medaka whose embryonic cells literally punctuate the dynamics of certain proteins involved in mitosis. 

In studying the timelapses of the developing mitotic spindle in live, transgenic medaka embryos, the experimenters discovered that large early embryos assemble unique spindles different from physical spindles.  In addition, Ran- GTP plays a decisive part in spindle conformation in early embryonic divisions, but the significance diminishes in after stage embryos. This is conceivably because the spindle structure is refashioned as cells get lower during development, though the exact reason is a subject for unborn exploration.

The experimenters also discovered that the early embryonic cells don't have a devoted spindle assembly checkpoint, which characterizes utmost physical cells, and which serves to insure that the chromosomes are duly aligned before isolation.  As Professor Kiyomitsu surmises," the checkpoint isn't active, and yet the chromosome aloneness are still veritably accurate. This could be explained by the fact that embryonic cells need to divide veritably snappily, but it's commodity that we want to study further."

While genetically modifying the medaka fish and studying the early embryos have led to new crucial perceptivity into embryonic mitosis, this is just the morning for Professor Kiyomitsu and the platoon.  In addition to questions related to the dwindling part of Ran- GTP in after stages and the missing spindle assembly checkpoint, he points to the satisfying harmony of cell divisions in the timelapses" The spindle conformation is characterized by a high degree of harmony, as the cells appear to be dividing in the sizes and defined directions, and the spindle is constantly in the center of the cells.  How can the spindle orient itself so regularly across the cells, and how is it suitable to find the center every time?"

Moving beyond the timelapses, the platoon also hopes to further solidify this new foundation with fresh medaka gene- lines to serve as models for exploration in embryonic cells, and at the same time optimize the genome editing process.  ultimately, the platoon wants to test for generalizability of their findings by studying embryonic mitosis in other organisms, and at a after stage, they want to explore the elaboration of spindle assembly and embryonic divisions, which would also contribute to a better understanding of mortal embryogenesis and to developing opinion and treatment of mortal gravidity. 

With this paper, we've created a solid foundation, but we've also opened a new frontier. Embryonic mitosis is beautiful, mysterious, and challenging to study, and we hope that with our work, we can ultimately get a little near to understanding the intricate processes at the morning of life. "

Professor Tomomi Kiyomitsu, elderly author of the study

Source

Journal reference

Kiyomitsu,A., etal.( 2024). Ran- GTP assembles a technical spindle structure for accurate chromosome isolation in medaka early embryos. Nature Dispatches. doi.org/10.1038/s41467-024-45251-w