The mammalian cerebral cortex, which is stratified into six layers, has functional domains that vertically span the six layers, thereby requiring tight interlaminar connectivity within a domain. The synaptic connections in individual layers are first broadly formed under predetermined programs and later reinforced between neurons which reside in the same functional domain via experience-dependent reorganization during the critical period. However, the molecular mechanisms that control these two processes within each layer are still unclear. Therefore, we performed a differential screen for candidates and found seven genes with layer-specific expression during postnatal development of cat visual cortex. Amyloid β (A4) precursor-like protein 1, a transmembrane protein mediating synaptogenesis, started dual-layer expression in layers 2/3 and 5 before the critical period, suggesting that it might execute coarse synapse formation of these layers. Stathmin-like 2 (STMN2/SCG10), which promotes microtubule turnover, was unique, as it dramatically shifted its dual-layer distribution from layers 2/3 and 5 to the deeper layers 4 and 6 at the onset of the critical period; it lost this new expression pattern in the adult. Surprisingly, brief dark rearing disturbed the shift in its dual-layer distribution around the onset of the critical period. Thus, by accelerating structural remodeling, STMN2 (SCG10) might launch experience-dependent reorganization of particular layers.