Defective neocortical development in Fyn-tyrosine-kinase-deficient mice.

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.