A septo-temporal molecular gradient of sfrp3 in the dentate gyrus differentially regulates quiescent adult hippocampal neural stem cell activation

Molecular Brain
Jiaqi SunK M Christian

Abstract

A converging body of evidence indicates that levels of adult hippocampal neurogenesis vary along the septo-temporal axis of the dentate gyrus, but the molecular mechanisms underlying this regional heterogeneity are not known. We previously identified a niche mechanism regulating proliferation and neuronal development in the adult mouse dentate gyrus resulting from the activity-regulated expression of secreted frizzled-related protein 3 (sfrp3) by mature neurons, which suppresses activation of radial glia-like neural stem cells (RGLs) through inhibition of Wingless/INT (WNT) protein signaling. Here, we show that activation rates within the quiescent RGL population decrease gradually along the septo-temporal axis in the adult mouse dentate gyrus, as defined by MCM2 expression in RGLs. Using in situ hybridization and quantitative real-time PCR, we identified an inverse septal-to-temporal increase in the expression of sfrp3 that emerges during postnatal development. Elimination of sfrp3 and its molecular gradient leads to increased RGL activation, preferentially in the temporal region of the adult dentate gyrus. Our study identifies a niche mechanism that contributes to the graded distribution of neurogenesis in the adult dentate g...Continue Reading

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Citations

Sep 15, 2016·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Rivka Noelanders, Kris Vleminckx
Dec 5, 2017·Disease Markers·Anja KafkaNives Pećina-Šlaus
Mar 17, 2016·Molecular Brain·Muriel D MardonesLorena Varela-Nallar
Oct 11, 2016·Molecular Neurobiology·Carlos Gonzalez-FernandezDaniel Garcia-Ovejero
Jan 10, 2018·Frontiers in Neuroscience·Franziska WigetIrmgard Amrein
May 26, 2020·Orphanet Journal of Rare Diseases·Leire Casas-FraileAmets Sáenz
Oct 3, 2018·Cerebral Cortex·Kirsten M LynchUNKNOWN Pediatric Imaging, Neurocognition and Genetics Study
Oct 13, 2020·Frontiers in Cell and Developmental Biology·Sebastian B ArredondoLorena Varela-Nallar

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Methods Mentioned

BETA
targeted lesions
PCR
in vitro transcription
dissection

Software Mentioned

Matlab
Reconstruct
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