Emergence of layer IV barrel cytoarchitecture is delayed in somatosensory cortex of GAP-43 deficient mice following delayed development of dendritic asymmetry

Abstract

The emergence of barrel cytoarchitecture in mouse somatosensory cortex is extremely well defined. However, mechanisms underlying the development of this cellular organization are not completely understood. While it is generally accepted that hollows emerge via passive displacement of cortical cells by dense thalamocortical afferent clusters in barrel centers, it is not known what causes cellular segregation of barrel sides and septa. Here, we hypothesized that the emergence of sides and septa is related to the progressive asymmetry of dendrites from the cells of the barrel side toward the barrel hollow during development. We tested this hypothesis in the barrel cortex of growth-associated protein-43 heterozygous mice (GAP43 (+/−) mice) that display a 2-day delay in retraction of septally oriented dendrites compared to (+/+) littermates. We predicted that this delayed retraction would result in a subsequent 2-day delay in the emergence of barrel sides and septa. Using cresyl violet staining of barrel cortex, we found that initial emergence of hollows was not different between GAP43 (+/−) mice and (+/+) littermate controls. However, the emergence of sides and septa was delayed by 2 days, supporting our hypothesis that the emergence of barrel sides and septa is related to, and perhaps reliant upon, the developmental step of dendritic orientation toward barrel hollows. This process, which is mechanistically distinct from the emergence of barrel hollows, is likely due to both active and passive events resulting from asymmetric cell orientation.

• GAP-43
• GAP43
• barrel cortex
• developmental cortical organization
• dendritic orientation
• autistic disorder