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

Abstract

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.