Life science
Medical & healthcare, Regenerative medicine

Discovery of a novel function of the cell nucleus that makes
internal organs left-right asymmetrical
Department of Biological Science, Graduate School of Science
Assistant Professor Mikiko Inaki

Researchmap https://researchmap.jp/mikikoinaki

Professor Kenji Matsuno

Researchmap https://researchmap.jp/chirality

Life science

Abstract
Our research group revealed that the nuclei of visceral muscle
cells that surround the digestive tract were densely aligned along
the anterior-posterior axis when the digestive tract becomes leftright asymmetric. This result was obtained by newly developedtechnologies using combination of time laps analyses and computer modeling, which allowed us to measure the movement of nuclei
in live Drosophila embryos. In addition, studies with genetic mutants in which the left-right asymmetry of the digestive tract wererandomized showed that nuclear alignment is necessary for theleft-right asymmetry of the digestive tract. These studies demonstrate that cell nucleus functions not only to store genes, but also
to utilize its physical strength to control morphological changes ofinternal organs.

▍ Background & Results
We revealed that the alignment of cell nuclei is necessary forthe internal organs to become left-right asymmetrical shape. Thenucleus is the largest organelle in eukaryotic cells. Since DNA(deoxyribonucleic acid), which constitute genes, exists in the nucleus, it has been thought that the storage of genes is the role ofthe nucleus. Here, our research group has developed a techniqueinvolving a time lapse analysis and computer modeling, which enable to measure the movement of nuclei in the digestive tract of live
Drosophila embryos (Fig.1). We found that the nuclei of visceralmuscle cells that cover the digestive tract are densely aligned in
the anterior-posterior direction. We clarified that this dense alignment is necessary for the shape of the digestive tract to be leftright asymmetric. Like the human internal organs, the Drosophila
digestive tract has a left-right asymmetrical shape. In the genetic
mutants in which the nuclei of muscle cells are not aligned, the leftright asymmetry of internal organs becomes randomized. Since
the nucleus is the hardest structure in the cell, it is thought that thenuclei densely aligned acts like a strut. The aligned nuclei supportthe structure of the digestive tract like a pole in a tent, and help tochange the structure left-right asymmetrically (Fig.2).

Fig.1 We developed a video analysis technique that enables time lapse three-dimensional measurement of the motility (A) and alignment (B) of the visceral muscle nuclei.

Fig.2 The nucleus is the hardest structure in the cell. It is aligned and acts like apillar as the role of 'building material'. Aligned nuclei support the structure of thegut and left-right asymmetrical shape changes during development.

▍ Significance of the research and Future perspective
These studies revealed that the cell nucleus functions not only tostore genes, but also to utilize its physical strength to control morphological changes of internal organs. It is expected that this result
can be applied as a technique for controlling the morphology ofregenerated organs using organoids.

P a t e n t
Tr e a t i s e

Shin, Dongsun; Inaki, Mikiko; Matsuno, Kenji et al. Collective nuclear behavior shapes bilateral nuclear symmetry for subsequent left right asymmetricmorphogenesis in Drosophila. Development. 2021; 148 (18): dev198507. doi: 10.1242/dev.198507

URL
K e y w o r d cell nucleus, left-right asymmetry, visceral muscle, digestive tract, drosophila