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Intermediate progenitors support migration of neural stem cells into dentate gyrus outer neurogenic niches.

Branden R Nelson | Rebecca D Hodge | Ray Am Daza | Prem Prakash Tripathi | Sebastian J Arnold | Kathleen J Millen | Robert F Hevner
eLife | 2020

The hippocampal dentate gyrus (DG) is a unique brain region maintaining neural stem cells (NCSs) and neurogenesis into adulthood. We used multiphoton imaging to visualize genetically defined progenitor subpopulations in live slices across key stages of mouse DG development, testing decades old static models of DG formation with molecular identification, genetic-lineage tracing, and mutant analyses. We found novel progenitor migrations, timings, dynamic cell-cell interactions, signaling activities, and routes underlie mosaic DG formation. Intermediate progenitors (IPs, Tbr2+) pioneered migrations, supporting and guiding later emigrating NSCs (Sox9+) through multiple transient zones prior to converging at the nascent outer adult niche in a dynamic settling process, generating all prenatal and postnatal granule neurons in defined spatiotemporal order. IPs (Dll1+) extensively targeted contacts to mitotic NSCs (Notch active), revealing a substrate for cell-cell contact support during migrations, a developmental feature maintained in adults. Mouse DG formation shares conserved features of human neocortical expansion.

Pubmed ID: 32238264 RIS Download

Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: P50 HD103524
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS085081
  • Agency: NIMH NIH HHS, United States
    Id: R21 MH087070
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS092339
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS099027
  • Agency: NIH HHS, United States
    Id: R21 OD023838

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