Gli3 is required for the specification and differentiation of preplate neurons

Abstract

During corticogenesis, the cerebral cortex develops a laminated structure which is essential for its function. Early born neurons of the preplate and its derivatives, the marginal zone (MZ) and the subplate (SP), serve as a framework during the cortical lamination process. Here, I report on defects in the generation and specification of these early born cortical neurons in extra-toes ( Xt J) mice which are defective for the Gli3 zinc finger transcription factor. The Gli3 mutation dramatically disrupts early steps in the cortical lamination process. The MZ, SP and the cortical plate (CP) do not form layers but cortical neurons are arranged in clusters. These defects start to become evident at E12.5 when the cortex forms several protrusions and the ventricular zone becomes undulated. At this stage, cortical progenitor cells start to loose their apical/basal cell polarity correlating with an ectopic expression of Wnt7b in the ventricular zone. In addition, the cellular composition of the preplate is severely altered. Cajal-Retzius cells are reduced in numbers while early born Calretinin + neurons are overproduced. These results show that multiple aspects of corticogenesis including the organization of the venticular zone, the apical/basal cell polarity of cortical progenitors and the differentiation of early born cortical neurons are affected in the Gli3 mutant.