Draxin regulates hippocampal neurogenesis in the postnatal dentate gyrus by inhibiting DCC-induced apoptosis
Autor: | Hideaki Tanaka, Helen M. Cooper, Masakado Kawata, Hiroshi Tawarayama, Ruhul Amin, Yohei Shinmyo, Shuntaro Ikawa, Hirohisa Yamada, Yuiko Morita-Fujimura |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Deleted in Colorectal Cancer Cellular differentiation Neurogenesis lcsh:Medicine Apoptosis Dependence receptor Hippocampal formation Biology Hippocampus Article 03 medical and health sciences Mice Neuroblast Neural Stem Cells medicine Animals RNA Small Interfering lcsh:Science Cells Cultured Mice Knockout Multidisciplinary Dentate gyrus lcsh:R fungi Membrane Proteins Cell Differentiation Granule cell DCC Receptor Cell biology Rats 030104 developmental biology medicine.anatomical_structure Caspases Dentate Gyrus Mutagenesis Site-Directed Intercellular Signaling Peptides and Proteins lcsh:Q RNA Interference |
Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) |
ISSN: | 2045-2322 |
Popis: | Hippocampal neurogenesis in the dentate gyrus (DG) is controlled by diffusible molecules that modulate neurogenic processes, including cell proliferation, differentiation and survival. To elucidate the mechanisms underlying hippocampal neurogenesis, we investigated the function of draxin, originally identified as a neural chemorepellent, in the regulation of neuronal survival in the DG. Draxin was expressed in Tbr2 (+) late progenitors and NeuroD1 (+) neuroblasts in the dentate granule cell lineage, whereas expression of its receptor DCC (deleted in colorectal cancer) was mainly detectable in neuroblasts. Our phenotypic analysis revealed that draxin deficiency led to enhanced apoptosis of DCC-expressing neuroblasts in the neurogenic areas. Furthermore, in vitro assays using a hippocampal neural stem/progenitor cell (HNSPC) line indicated that draxin inhibited apoptosis in differentiating HNSPCs, which express DCC. Taken together, we postulate that draxin plays a pivotal role in postnatal DG neurogenesis as a dependence receptor ligand for DCC to maintain and promote survival of neuroblasts. |
Databáze: | OpenAIRE |
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