Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone
Vivianne Morrison,
Matthew Houpert,
Jonathan Trapani,
Asa Brockman,
Philip Kingsley,
Ketaki Katdare,
Hillary Layden,
Gabriela Nguena-Jones,
Alexandra Trevisan,
Kathleen Maguire-Zeiss,
Lawrence Marnett,
Gregory Bix,
Rebecca Ihrie,
Bruce Carter
Affiliations
Vivianne Morrison
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA; Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA
Matthew Houpert
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA
Jonathan Trapani
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA
Asa Brockman
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37235, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA
Philip Kingsley
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA
Ketaki Katdare
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA
Hillary Layden
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA
Gabriela Nguena-Jones
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA
Alexandra Trevisan
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Kathleen Maguire-Zeiss
Department of Neuroscience, Georgetown University, Washington, DC 20057, USA
Lawrence Marnett
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN 37235, USA; A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA
Gregory Bix
Center for Clinical Neuroscience Research, Tulane University, New Orleans, LA 70118, USA
Rebecca Ihrie
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37235, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA
Bruce Carter
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA; Corresponding author
Summary: Microglia are the primary phagocytes in the central nervous system and clear dead cells generated during development or disease. The phagocytic process shapes the microglia phenotype, which affects the local environment. A unique population of microglia resides in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence the neurogenic niche is not well understood. Here, we demonstrate that phagocytosis contributes to a pro-neurogenic microglial phenotype in the V-SVZ and that these microglia phagocytose apoptotic cells via the engulfment receptor Jedi-1. Deletion of Jedi-1 decreases apoptotic cell clearance, triggering a neuroinflammatory microglia phenotype that resembles dysfunctional microglia in neurodegeneration and aging and that reduces neural precursor proliferation via elevated interleukin-1β signaling; interleukin-1 receptor inhibition rescues precursor proliferation in vivo. Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to the maintenance of a pro-neurogenic phenotype in the developing V-SVZ.
