Cytoarchitecture and Transcriptional Profiles of Neocortical Malformations in Inbred Mice

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Abstract
Malformations of neocortical development are associated with cognitive dysfunction and increased susceptibility to epileptogenesis. Rodent models are widely used to study neocortical malformations and have revealed important genetic and environmental mechanisms that contribute to neocortical development. Interestingly, several inbred mice strains commonly used in behavioral, anatomical, and/or physiological studies display neocortical malformations. In the present report we examine the cytoarchitecture and myeloarchitecture of the neocortex of 11 inbred mouse strains and identified malformations of cortical development, including molecular layer heterotopia, in all but one strain. We used in silico methods to confirm our observations and determined the transcriptional profiles of cells found within heterotopia. These data indicate cellular and transcriptional diversity present in cells in malformations. Furthermore, the presence of dysplasia in nearly every inbred strain examined suggests that malformations of neocortical development are a common feature in the neocortex of inbred mice.