Unknown,Transcriptomics,Genomics,Proteomics

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Combined multiphoton live-cell imaging and molecular systems approaches reveal mosaic contribution of dynamic transiently signaling INPs to the adult Dentate Gyrus NSC niche

ABSTRACT: Here we directly compare for the first time how the longstanding static model of mouse Dentate Gyrus (DG) development compares with a comprehensive high-resolution live-cell multiphoton (live-MPM) imaging approach. We took advantage of multiple fluorescent protein-based cell-type specific reporters to identify Neural Stem Cells (NSC), Intermediate Neurogenic Progenitors (INPs), and Granule Neurons (GNs) to generate live 4D cellular datasets across embryonic, postnatal and adult ages. Live-MPM revealed that INPs and NSCs migrated long distances along multiple routes to seed the SGZ from multiple directions, and from mosaic progenitor zones along the septo-temporal axis of the hippocampus. We found that dynamic INPs processes and interactions contributed to the architecture of both transient and permanent NSC niches during embryonic development, and that INP cellular plasticity is maintained in the adult SGZ NSC niche. We also used a Molecular Systems (MS) approach to determine the basis for maintained INP cellular plasticity that revealed an overlapping signaling network infrastructure based largely on Rho-family mediated regulation of cytoskeletal dynamics. Our combined strategies revealed that dynamic INPs are a major molecular signaling transition state in the adult SGZ, and that Tbr2 expression defines the initial stage of GN commitment. Our novel findings reveal fundamental new insight into one of the most well studied brain regions key for normal cognitive function, and the importance of analyzing the development of live stem cell niches in vivo. In concert with live-cell imaging, we used microarray analysis to identify genes that may be involved in the development of the Dentate Gyrus NSC niche.

ORGANISM(S): Mus musculus

SUBMITTER: James MacDonald

PROVIDER: E-GEOD-50148 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Combined multiphoton live-cell imaging and molecular systems approaches reveal mosaic contribution of dynamic transiently signaling INPs to the adult Dentate Gyrus NSC niche

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