Defects in reciprocal projections between the thalamus and cerebral cortex in the early development of Fezl-deficient mice.

Fez-like (Fezl), the forebrain embryonic zinc finger-like protein, is a transcriptional repressor selectively expressed in the deep layers of the developing cortex. We examined the thalamocortical and corticofugal pathways in Fezl-deficient fetal mice by using immunohistochemistry and by axonal labeling with the lipophilic dyes DiI and DiA, with special attention to the spatiotemporal relation between thalamocortical and corticofugal axons. In normal mice, thalamic and cortical axons meet in the internal capsule between embryonic day (E) 13.5 and E14.5 and fasciculate with each other as they extend to their targets, the cortex and thalamus, respectively. In Fezl-deficient mice, most of the thalamic and cortical axons stop in the internal capsule and at the pallial-subpallial boundary at E14.5, respectively. This abnormality is transient, and the thalamic and cortical axons reach their targets at E15.5, although the number of thalamic axons is remarkably reduced in the cortical anlage. Double labeling with DiI and DiA demonstrated close apposition of the thalamic and cortical axons in the subpallium and pallium as well as in the external capsule of this mutant after E15.5. Because the expression of genes that define the pallial-subpallial boundary and guidance molecules of thalamocortical axons did not show remarkable changes in Fezl-deficient mice, abnormal formation of thalamocortical pathway in this mutant may be caused by the defect of axons of cortical efferent neurons that express Fezl.