Roles of ZBTB20 in the specification of upper layer neurons and astrocytes in the neocortex
ZBTB20; neocortex; development; neuron specification; astrogliogenesis
Organization of neocortical circuits is critical for sensory perception, learning and multisensory
integration. In the primary somatosensory area (S1) layer IV neurons receive thalamic inputs and
synapse onto layer II/III neurons. These superficial neurons may connect other neurons within S1 and
within other areas in the ipsi or contralateral hemisphere, thus cooperating to select an
interpretation consistent with their various cortical and subcortical inputs. Here we show that
expression of the transcription factor Zinc Finger And BTB Domain-Containing Protein 20 (Zbtb20) in
neocortical progenitors is necessary and sufficient to regulate the generation and hiring patterns of
upper layer neurons. Conditional deletion of this gene in progenitors leads to an increase in the
number and radial occupancy of RORb+/layer IV at the expense of Brn2+/layers II/III neurons. This
change in the laminar organization of the neocortex is accompanied by an expansion of thalamic
axonal arborization and barrel area in S1. Furthermore, upper layer neurons increase their intra-
hemispheric axonal projections, while reducing contralateral innervation in the absence of Zbtb20
expression. These alterations are also observed, albeit at a lesser extent, after Zbtb20 deletion in
post-mitotic neurons, indicating that Zbtb20 act at sequential stages of the lineage progression of
neocortical progenitors, fine-tuning neuronal fates in upper cortical layers and contributing to the
proper wiring of callosal projecting neurons (CPNs). Besides these effects in CPN fate specification,
we also show that ZBTB20 regulates astrogliogenesis in a time-specific fashion. ZBTB20
overexpression at E14, but not at E16, increases neocortical astrogliogenesis, whereas expression of
a dominant-negative (DN) ZBTB20 at E16, but not E14, reduces astrogliogenesis. Altogether, our
results indicate that ZBTB20 is an important regulator of cell type/subtype specification in the
developing neocortex.