A Common Embryonic Origin of Stem Cells Drives Developmental and Adult Neurogenesis

Highlights

• The Hopx-CreER^T2 line can label an embryonic origin of adult dentate neural progenitors

• Hopx⁺ dentate progenitors exhibit constant lineage specification across development

• Developmental and adult dentate neurogenesis are one continuous process

• Hopx⁺ dentate progenitors retain common molecular signatures across development

Summary

New neurons arise from quiescent adult neural progenitors throughout life in specific regions of the mammalian brain. Little is known about the embryonic origin and establishment of adult neural progenitors. Here, we show that Hopx⁺ precursors in the mouse dentate neuroepithelium at embryonic day 11.5 give rise to proliferative Hopx⁺ neural progenitors in the primitive dentate region, and they, in turn, generate granule neurons, but not other neurons, throughout development and then transition into Hopx⁺ quiescent radial glial-like neural progenitors during an early postnatal period. RNA-seq and ATAC-seq analyses of Hopx⁺ embryonic, early postnatal, and adult dentate neural progenitors further reveal common molecular and epigenetic signatures and developmental dynamics. Together, our findings support a “continuous” model wherein a common neural progenitor population exclusively contributes to dentate neurogenesis throughout development and adulthood. Adult dentate neurogenesis may therefore represent a lifelong extension of development that maintains heightened plasticity in the mammalian hippocampus.