Altered Molecular Regionalization and Normal Thalamocortical Connections in Cortex-SpecificPax6Knock-Out Mice

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Abstract
Transcription factor Pax6 exerts a prominent rostrolateralhigh to caudomediallow expression gradient in the cortical progenitors and have been implicated in regulation of area identity in the mammalian cortex. Herein, we analyzed the role of Pax6 in molecular arealization and development of thalamocortical connections in the juvenile cortex-specific conditional Pax6 knock-out mice (Pax6cKO). Using a set of molecular markers of positional identity (Id2, Cadherin6, COUP-TF1, RZRβ, and EphA7), we show that, in the juvenile Pax6cKO, the relative size of caudal cortical areas (putative visual and somatosensory) are mildly enlarged, whereas the rostral domain (putative motor) is severely reduced. Despite the rostral shift of graded expression of areal markers, the distribution of area-specific thalamocortical and corticofugal projections appear normal in the Pax6cKO. This indicates that change of the size of cortical areas is not accompanied by a change in cortical identity. We show furthermore that, despite a severe depletion of supragranular cortical layers and accumulation of cells along the pallial–subpallial boundary, thalamocortical fibers establish a periphery-related pattern of the somatosensory cortex in normal position in Pax6cKO. Our findings indicate that Pax6 expression gradients in cortical progenitors do not directly impart thalamocortical or corticofugal areal identity.