[S7.4]: Creating the cortex and the hippocampal organizer

The earliest step in creating the cerebral cortex is the specification of telencephalic neuroepithelium to a cortical fate. To date, several transcription factors have been identified which are critical for particular aspects of cortical development. Of these, Lhx2 appears to be act at the earliest stage of specifying the cortical primordium. We find that in the Lhx2 standard knockout, the entire cortical primordium is deleted. Instead, there is an expansion of the hem and the antihem, tissue that normally flank the cortical primordium. Using embryonic stem cell chimeras, we tested whether this is due to a cell-autonomous role of Lhx2 in the dorsal telencephalic neuroepithelium. We find that Lhx2 mutant patches take on either of two alternative fates in the chimeric dorsal telencephalon: laterally, they take on the identity of the antihem, whereas medially they differentiate into cortical hem tissue. Lhx2, therefore, is required to create the cortex, functioning as a “cortical selector” gene. The ectopic patches of cortical hem act as “hippocampal organizers,” patterning the adjacent wild-type cortex into multiple ectopic hippocampi. Each of these shows appropriate field-specific molecular and structural features, including additional radial glial palisades, which are essential for proper cell migration. This provides definitive functional evidence for the cortical hem as a secondary organizer in the telencephalon.