Foxg1 Confines Cajal-Retzius Neuronogenesis and Hippocampal Morphogenesis to the Dorsomedial Pallium

It has been suggested that cerebral cortex arealization relies on positional values imparted to early cortical neuroblasts by transcription factor genes expressed within the pallial field in graded ways. Foxg1, encoding for one of these factors, previously was reported to be necessary for basal ganglia morphogenesis, proper tuning of cortical neuronal differentiation rates, and the switching of cortical neuroblasts from early generation of primordial plexiform layer to late production of cortical plate. Being expressed along a rostral/lateralhigh- to-caudal/mediallow gradient, Foxg1, moreover, could contribute to shaping the cortical areal profile as a repressor of caudomedial fates. We tested this prediction by a variety of approaches and found that it was correct. We found that overproduction of Cajal-Retzius neurons characterizing Foxg1-/- mutants does not arise specifically from blockage of laminar histogenetic progression of neocortical neuroblasts, as reported previously, but rather reflects lateral-to-medial repatterning of their cortical primordium. Even if lacking a neocortical plate, Foxg1-/- embryos give rise to structures, which, for molecular properties and birthdating profile, are highly reminiscent of hippocampal plate and dentate blade. Remarkably, in the absence of Foxg1, additional inactivation of the medial fates promoter Emx2, although not suppressing cortical specification, conversely rescues overproduction of Reelinon neurons.

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