Figure 1.

LHX1 regulates the migration and survival of immature preoptic area (POA)-derived interneurons destined for the cerebral cortex.

(A) The population of Hmx3-expressing cells in the POA gives rise to interneurons destined for the cerebral cortex and other brain regions as well as to local cells remaining on site. POA-derived interneurons preferentially are using the superficial migratory stream (SMS, blue line) to migrate through the basal telencephalon into the cortex (Lhx1 WT). A small proportion is also using the deep migratory stream (DMS, green line) through the MGE. Bidirectional EPHA4-EFNB3 signaling contributes to the separation and channeling of immature interneurons into superficial migrating EFNB3-positive cells (blue cells) and deep migrating EPHA4-positive cells (green cells). Post-mitotic deletion of Lhx1 in Hmx3-expressing cells (Lhx1 KO) lead to an enhanced overall cell number and an increased proportion of POA-derived interneurons using the DMS. As possible reason, Lhx1 deficiency promotes higher levels of EPHA4 expression and reduced EFNB3 levels in embryonic POA cells. (B) Prior to migration LHX1 restrict cell survival (indicated by red cells) possibly by repressing pro-survival genes like Bcl2 and Bcl6 and promoting pro-apoptotic Unc5b expression which is misregulated in Lhx1 KO.