A role of Lhx2 in the migration and axonal projection of cortical postmitotic neurons in the cortical upper layer of the mouse neocortex.

The transcription factor LHX2 contains a LIM domain and plays an important role in the development of the vertebrate nervous system. Although much research has been conducted on the function of Lhx2 during cerebral development, its role in postmitotic neuron differentiation in the cerebral cortex remains unknown. Therefore, this study was conducted to determine the function of Lhx2 in dynamic and elaborate developmental processes, including neurogenesis. We first created and confirmed an Lhx2-BAC Gfp transgenic model to three-dimensionally confirm the spatiotemporal expression pattern of Lhx2 during brain development. On this basis, we used the bilateral in utero electroporation technique to express the dominant-negative form of LHX2. LHX2 was confirmed to be important for the migration and callosal projection of postmitotic neurons that form the upper layer of the cerebral cortex during neurogenesis. Additionally, transcriptome analysis confirmed that LHX2 affected the genes involved in neuronal migration and axonal projection. We demonstrated that Lhx2 is important for postmitotic neurons in the cerebral cortex, which migrate to normal positions and extend nerve axons. Taken together, our findings can provide important clues to understanding the relationship between human Lhx2 gene mutations and brain developmental diseases.

ZBTB20 is crucial for the specification of a subset of callosal projection neurons and astrocytes in the mammalian neocortex.

Neocortical progenitor cells generate subtypes of excitatory projection neurons in sequential order followed by the generation of astrocytes. The transcription factor zinc finger and BTB domain-containing protein 20 (ZBTB20) has been implicated in regulation of cell specification during neocortical development. Here, we show that ZBTB20 instructs the generation of a subset of callosal projections neurons in cortical layers II/III in mouse. Conditional deletion of Zbtb20 in cortical progenitors, and to a lesser degree in differentiating neurons, leads to an increase in the number of layer IV neurons at the expense of layer II/III neurons. Astrogliogenesis is also affected in the mutants with an increase in the number of a specific subset of astrocytes expressing GFAP. Astrogliogenesis is more severely disrupted by a ZBTB20 protein containing dominant mutations linked to Primrose syndrome, suggesting that ZBTB20 acts in concert with other ZBTB proteins that were also affected by the dominant-negative protein to instruct astrogliogenesis. Overall, our data suggest that ZBTB20 acts both in progenitors and in postmitotic cells to regulate cell fate specification in the mammalian neocortex.