Draxin regulates hippocampal neurogenesis in the postnatal dentate gyrus by inhibiting DCC-induced apoptosis.

Abstract	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.
Authors	Hiroshi Tawarayama, Hirohisa Yamada, Ruhul Amin, Yuiko Morita-Fujimura, Helen M Cooper, Yohei Shinmyo, Masakado Kawata, Shuntaro Ikawa, Hideaki Tanaka
Journal	Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 840 (01 16 2018) ISSN: 2045-2322 [Electronic] England
PMID	29339781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	DCC Receptor Dcc protein, rat Intercellular Signaling Peptides and Proteins Membrane Proteins RNA, Small Interfering draxin protein, mouse neogenin Caspases
Topics	Animals Apoptosis Caspases (metabolism) Cell Differentiation Cells, Cultured DCC Receptor (antagonists & inhibitors, genetics, metabolism) Dentate Gyrus (metabolism) Hippocampus (metabolism) Intercellular Signaling Peptides and Proteins (chemistry, genetics, metabolism) Membrane Proteins (antagonists & inhibitors, genetics, metabolism) Mice Mice, Knockout Mutagenesis, Site-Directed Neural Stem Cells (cytology, metabolism) Neurogenesis RNA Interference RNA, Small Interfering (metabolism) Rats

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