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Published on: May 12, 2015
Defective neocortical development in Fyn-tyrosine-kinase-deficient mice
Shigeki Yuasa1, Kotaro Hattori, Takeshi Yagi
1Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. yuasa-s@ncnp.go.jp
Abstract:
Fyn tyrosine kinase is involved in the tyrosine-phosphorylation of Disabled-1 in the Reelin signaling pathway, and absence of Fyn is expected to result in a reeler-like phenotype. Thus, this study investigated neocortical development in Fyn-deficient mice. Bromodeoxyuridine labeling revealed the under-migration of later-generated neurons despite the normal placement of earlier-generated neurons. Calbindin- and alpha-calcium/calmodulin-dependent protein kinase II-immunohistochemistry showed that layer II-III neurons were aberrantly stratified, but the neurons in the deeper layers showed little evidence of abnormality. Fyn was intensely expressed in the leading process of migratory cortical neurons generated in the later stage. These findings strongly suggest that Fyn is required for the migration of later-generated neurons, but that it is dispensable for the Reelin-dependent inside-out layer formation.
Insights
Fyn tyrosine kinase is crucial for the migration of later-born neurons in the developing neocortex. Its absence leads to under-migration and abnormal layering, but does not disrupt Reelin-dependent development.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Fyn tyrosine kinase plays a role in the Reelin signaling pathway.
- Absence of Fyn is hypothesized to cause a reeler-like phenotype, affecting neocortical development.
Purpose of the Study:
- To investigate the role of Fyn tyrosine kinase in neocortical development.
- To determine if Fyn deficiency impacts neuronal migration and layer formation.
Main Methods:
- Utilized Fyn-deficient mice models.
- Employed Bromodeoxyuridine labeling to track neuronal migration.
- Conducted Calbindin and alpha-calcium/calmodulin-dependent protein kinase II immunohistochemistry to assess neuronal stratification.
Main Results:
- Bromodeoxyuridine labeling showed under-migration of later-generated neurons.
- Layer II-III neurons exhibited aberrant stratification, while deeper layers were largely unaffected.
- Fyn expression was observed in the leading process of migratory cortical neurons.
Conclusions:
- Fyn tyrosine kinase is essential for the migration of later-generated cortical neurons.
- Fyn is dispensable for the Reelin-dependent inside-out cortical layer formation.
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