Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, United States; Department of Neurological Surgery, University of Washington, Seattle, United States
Rebecca D Hodge
Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, United States
Ray AM Daza
Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, United States
Prem Prakash Tripathi
Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, United States
Sebastian J Arnold
Institute of Experimental and Clinical Pharmacology and Toxicology, Freiburg, Germany; Signaling Research Centers BIOSS and CIBSS, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, United States; Department of Pediatrics, University of Washington, Seattle, United States
Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, United States; Department of Neurological Surgery, University of Washington, Seattle, United States
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.
