Age-Dependent Netrin-1 Signaling Regulates NG2+ Glial Cell Spatial Homeostasis in Normal Adult Gray Matter.
Neuron-glial antigen 2-positive (NG2(+)) glial cells are the most proliferative glia type in the adult CNS, and their tile-like arrangement in adult gray matter is under tight regulation. However, little is known about the cues that govern this unique distribution. To this end, using a NG2(+) glial cell ablation model in mice, we examined the repopulation dynamics of NG2(+) glial cells in the mature and aged mice gray matter. We found that some resident NG2(+) glial cells that escaped depletion rapidly enter the cell cycle to repopulate the cortex with altered spatial distribution. We reveal that netrin-1 signaling is involved in the NG2(+) glial cell early proliferative, late repopulation, and distribution response after ablation in the gray matter. However, ablation of NG2(+) glial cell in older animals failed to stimulate a similar repopulation response, possibly because of a decrease in the sensitivity to netrin-1. Our findings indicate that endogenous netrin-1 plays a role in NG2(+) glial cell homeostasis that is distinct from its role in myelination.
Graduate Program in Genetics and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11794.
Fikri
F
Birey
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11794 adan.aguirre@stonybrook.edu.
Adan
A
Aguirre
D000375:Aging; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D066128:Gray Matter / Q000166:cytology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D047468:Immunoprecipitation; D019394:Ki-67 Antigen / Q000378:metabolism; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009414:Nerve Growth Factors / Q000276:immunology / Q000378:metabolism*; D000075388:Netrin-1; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000276:immunology / Q000378:metabolism*; D000099216:Chondroitin Sulfate Proteoglycan 4
D000906:Antibodies; D000941:Antigens; D001973:Bromodeoxyuridine; D019394:Ki-67 Antigen; D009414:Nerve Growth Factors; D000075388:Netrin-1; D018809:Proliferating Cell Nuclear Antigen; D011509:Proteoglycans; D022661:RNA, Untranslated; D020796:Receptor, Platelet-Derived Growth Factor alpha; D025521:Tumor Suppressor Proteins; D000099216:Chondroitin Sulfate Proteoglycan 4; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C000617353:Ntn1 protein, mouse
NG2+ glia; Netrin-1; homeostasis