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Age-specific function of α5β1 integrin in microglial migration during early colonization of the developing mouse
Sophie Marie-Thérèse Smolders1,2,3, Nina Swinnen1, Sofie Kessels1
1UHasselt, BIOMED, Diepenbeek, Belgium.
Abstract:
Microglia, the immune cells of the central nervous system, take part in brain development and homeostasis. They derive from primitive myeloid progenitors that originate in the yolk sac and colonize the brain mainly through intensive migration. During development, microglial migration speed declines which suggests that their interaction with the microenvironment changes. However, the matrix-cell interactions allowing dispersion within the parenchyma are unknown. Therefore, we aimed to better characterize the migration behavior and to assess the role of matrix-integrin interactions during microglial migration in the embryonic brain ex vivo. We focused on microglia-fibronectin interactions mediated through the fibronectin receptor α5β1 integrin because in vitro work indirectly suggested a role for this ligand-receptor pair. Using 2-photon time-lapse microscopy on acute ex vivo embryonic brain slices, we found that migration occurs in a saltatory pattern and is developmentally regulated. Most importantly, there is an age-specific function of the α5β1 integrin during microglial cortex colonization. At embryonic day (E) 13.5, α5β1 facilitates migration while from E15.5, it inhibits migration. These results indicate a developmentally regulated function of α5β1 integrin in microglial migration during colonization of the embryonic brain.
Insights
Microglia migration in the embryonic brain is saltatory and developmentally regulated. The α5β1 integrin switches from facilitating to inhibiting migration, impacting brain colonization.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia, the central nervous system's immune cells, are crucial for brain development and homeostasis.
- These cells originate from yolk sac progenitors and migrate extensively to colonize the embryonic brain.
- Declining microglial migration speed during development suggests changing microenvironmental interactions, but parenchymal dispersion mechanisms remain unclear.
Purpose of the Study:
- To characterize microglial migration behavior in the embryonic brain ex vivo.
- To investigate the role of matrix-integrin interactions, specifically microglia-fibronectin interactions via α5β1 integrin, in this process.
Main Methods:
- Utilized 2-photon time-lapse microscopy on acute ex vivo embryonic brain slices.
- Focused on analyzing microglial migration patterns and the function of the α5β1 integrin at different embryonic stages.
Main Results:
- Microglial migration exhibits a saltatory pattern and is developmentally regulated.
- The α5β1 integrin demonstrates an age-specific function: it facilitates migration at embryonic day (E) 13.5 but inhibits it from E15.5 onwards.
- This dynamic role of α5β1 integrin influences microglial cortex colonization.
Conclusions:
- Microglial migration within the embryonic brain is a complex, developmentally controlled process.
- The α5β1 integrin plays a critical, stage-dependent role in regulating microglial migration during brain colonization.
- Understanding these matrix-cell interactions is key to deciphering microglial development and function.
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