Phagocytic activity of neuronal progenitors regulates adult neurogenesis

• Published in: Nature cell biology Vol. 13; no. 9; pp. 1076 - 1083
• Main Authors: Chen, Yubo, Ravichandran, Kodi S, Kipnis, Jonathan, Lu, Zhenjie, Elliott, Michael R, Walsh, James T, Klibanov, Alexander L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2011; Nature Publishing Group
• Subjects: 631/136/368/2431; 631/80/313/1727; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Apoptosis; Biomedical and Life Sciences; Brain - cytology; Brain - metabolism; Cancer Research; Cell Biology; Cell Differentiation; Cell Movement; Cell Proliferation; Cells, Cultured; Developmental Biology; Female; Immunohistochemistry; letter; Life Sciences; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Confocal; Microtubule-Associated Proteins - metabolism; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurogenesis; Neurons - cytology; Neurons - metabolism; Neuropeptides - metabolism; Phagocytes - cytology; Phagocytes - metabolism; Phagocytosis; Proteins; Stem Cells; Time Factors; United States; United States > US; Virginia; China
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb2299

Whereas thousands of new neurons are generated daily during adult life, only a fraction of them survive and become part of neural circuits; the rest die, and their corpses are presumably cleared by resident phagocytes. How the dying neurons are removed and how such clearance influences neurogenesis are not well understood. Here, we identify an unexpected phagocytic role for the doublecortin (DCX)-positive neuronal progenitor cells during adult neurogenesis. Our in vivo andex vivo studies demonstrate that DCX+ cells comprise a significant phagocytic population within the neurogenic zones. Intracellular engulfment protein ELMO1, which promotes Rac activation downstream of phagocytic receptors, was required for phagocytosis by DCX+ cells. Disruption of engulfment in vivo genetically (in Elmo1-null mice) or pharmacologically (in wild-type mice) led to reduced uptake by DCX+ cells, accumulation of apoptotic nuclei in the neurogenic niches and impaired neurogenesis. Collectively, these findings indicate a paradigm wherein DCX+ neuronal precursors also serve as phagocytes, and that their phagocytic activity critically contributes to neurogenesis in the adult brain.