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Rapalog-induced cell adhesion molecule inhibits mesoderm migration in Xenopus embryos by increasing frequency of
Chisa Usami1,2, Hidehiko Inomata1,2
1Axial Pattern Dynamics Team, Center for Biosystems Dynamics Research, RIKEN, Kobe, Japan.
Abstract:
During the gastrula stage of Xenopus laevis, mesodermal cells migrate on the blastocoel roof (BCR) toward the animal pole. In this process, mesodermal cells directly adhere to the BCR via adhesion molecules, such as cadherins, which in turn trigger a repulsive reaction through factors such as Eph/ephrin. Therefore, the mesoderm and BCR repeatedly adhere to and detach from each other, and the frequency of this adhesion is thought to control mesoderm migration. Although knockdown of cadherin or Eph/ephrin causes severe gastrulation defects, these molecules have been reported to contribute not only to boundary formation but also to the internal function of each tissue. Therefore, it is possible that the defect caused by knockdown occurs due to tissue function abnormalities. To address this problem, we developed a method to specifically induce adhesion between different tissues using rapalog (an analog of rapamycin). When adhesion between the BCR and mesoderm was specifically enhanced by rapalog, mesoderm migration was strongly suppressed. Furthermore, we confirmed that rapalog significantly increased the frequency of adhesion between the two tissues. These results support the idea that the adhesion frequency controls mesoderm migration, and demonstrate that our method effectively enhances adhesion between specific tissues in vivo.
Insights
Mesodermal cell migration during Xenopus gastrulation is controlled by adhesion frequency to the blastocoel roof. Enhancing this adhesion with rapalog suppressed migration, confirming the frequency
Area of Science:
- Developmental biology
- Cell biology
- Molecular biology
Background:
- Mesodermal cell migration is crucial for gastrulation in Xenopus laevis.
- Cell-cell adhesion molecules like cadherins and Eph/ephrin signaling regulate mesoderm migration on the blastocoel roof (BCR).
- Previous studies using knockdown methods showed gastrulation defects, but distinguishing between boundary formation and tissue function roles was challenging.
Purpose of the Study:
- To investigate the role of adhesion frequency in controlling mesodermal cell migration.
- To develop a novel method for specifically inducing adhesion between tissues in vivo.
- To validate the hypothesis that adhesion frequency dictates mesoderm migration dynamics.
Main Methods:
- Development of a rapalog-inducible system to specifically enhance adhesion between the BCR and mesodermal cells.
- Utilizing rapalog (an analog of rapamycin) to control the degree of inter-tissue adhesion.
- Quantifying the effects of enhanced adhesion on mesodermal cell migration speed and frequency of cell-tissue interaction.
Main Results:
- Specific enhancement of adhesion between the BCR and mesoderm using rapalog led to significant suppression of mesodermal cell migration.
- Rapalog treatment demonstrably increased the frequency of adhesion events between the two tissues.
- The study provides direct evidence linking increased adhesion frequency to reduced cell migration.
Conclusions:
- Adhesion frequency between mesodermal cells and the BCR is a critical regulator of mesoderm migration during gastrulation.
- The developed rapalog-based method offers a precise tool to study in vivo tissue interactions.
- This approach overcomes limitations of genetic knockdown by specifically manipulating adhesion without affecting general tissue function.
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