The Way Mouse Embryos Determine Between The Left And Right Sides
The process through which small hairs in embryos perceive fluid movement has been identified by biologists from RIKEN, which ultimately results in the development of differences between the left and right sides of the embryo. This discovery not only settles a longstanding argument but also provides valuable insights for studying disorders that occur due to the malfunctioning of this mechanism.
How the differences between the left and right sides develop in embryos
When observed externally, it is typically difficult to differentiate between the left and right sides of vertebrate bodies. However, the scenario is contrasting inside the body where various organs such as the heart, liver, and spleen situate on either side of the central axis that separates left and right.
In contrast, embryos commence as collections of cells that are symmetrical. The process of how dissimilarities arise between the left and right sides of embryos has been a subject of research interest for a long time.
In a mouse embryo, minuscule hair-like structures called cilia rotate in a clockwise direction, creating a flow of fluid that moves towards the left in the surrounding environment. Immotile cilia, fixed in position and located on both sides of the moving cilia, perceive the flow of fluid generated by the latter. The perception of fluid movement triggers dissimilar developmental pathways between the left and right sides of the embryo.
The manner how the immotile cilia sense the fluid flow
Nevertheless, there is a disagreement regarding the mechanism by which immotile cilia detect the flow of fluid. Two hypotheses have been put forward: the first proposes that the flow of fluid is sensed by the chemicals present in it, while the second suggests that it is detected through the mechanical force exerted by the flow. However, to date, there has been no experimental evidence to confirm which hypothesis is correct.
The controversy has been resolved by Hiroshi Hamada and Takanobu Katoh, along with their colleagues at the RIKEN Center for Biosystems Dynamics Research, who have demonstrated through their research that the cilia in mouse embryos sense the fluid flow mechanically.
By utilizing a laser beam, the research team exerted control over a solitary cilium and noted a signal that involved calcium ions. This experiment confirmed that the mechanical stimulation of a single cilium is sufficient to establish the left-right asymmetry in embryos.
Employing sophisticated microscopy methods, they also detected that the cilia on the left and right sides bend in opposite directions. In addition, they concluded that the cilia detect the direction of bending due to the uneven distribution of channels within them. Consequently, calcium signals only generate when fluid flows in a specific direction. Which elucidates why only the cilia on the left side of an embryo activate.
The impact of discovery
According to Katoh, the main author of a paper published in Science, “they have provided a conclusive response to a vital inquiry about determining left-right asymmetry. The inquiry was why the left side solely trigger by leftward nodal flow. This breakthrough is a significant advancement in understanding the process of left-right asymmetry establishment“.
Katoh also mentioned that “these findings may have practical implications. The research results could provide valuable knowledge for studying the organogenesis process and could potentially aid in developing treatments for conditions related to cilia malfunction“.
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