The Genetic Basis of Hippocampal Development

The hippocampus is critical for an array of cognitive functions arising from its complex substructure and connectivity. Important insights into hippocampal field specification emerged from classical studies that examined mice lacking particular transcription factors or signaling molecules. Recent high-throughput bioinformatics approaches have led to fresh perspectives on these findings. This review offers a semihistorical timeline of the discovery of the hippocampal organizer and examines the interplay of factors that position this structure. We compare the rich body of literature in the mouse with studies in nonmammalian vertebrates and in human-derived organoid models that reveal commonalities in the mechanisms that induce specific hippocampal fates. We also examine the regulation of neurogenesis versus gliogenesis and the migration of different cell types in the hippocampus. We discuss open questions that arise from discoveries made over the past three decades, and suggest hypotheses or approaches that will expand our understanding of the choreography of hippocampal development.