title: Conditional rod photoreceptor ablation reveals Sall1 as a microglial marker and regulator of microglial morphology in the retina.
abstract: Neurodegeneration has been shown to induce microglial activation and the infiltration of monocyte-derived macrophages into the CNS, resulting in the coexistence of these two populations within the same lesion, though their distinct features remain elusive. To investigate the impact of rod photoreceptor degeneration on microglial activation, we generated a toxin-mediated genetic model of rod degeneration. Rod injury induced microglial proliferation and migration toward the photoreceptors. Bone marrow transplantation revealed the invasion of monocyte-derived macrophages into the retina, with microglia and the infiltrating macrophages showing distinct distribution patterns in the retina. By comparing the gene expression profiles of the activated microglia and infiltrating macrophages, we identified microglia-specific genes, including Ak1, Ctsf, Sall1, Phlda3, and Spns2. An analysis of Sall1gfp knock-in mice showed GFP expression in the microglia of developing and mature healthy retinas. DTA injury induced the expansion of Sall1gfp(+) microglia, whereas Ly6C(+) monocyte-derived macrophages were mostly Sall1gfp(-) , supporting the idea that Sall1 is exclusively expressed in microglia within the retinal phagocyte pool. We evaluated the contribution of microglia to the phagocyte pool in rd1 mutant retinas and found that Sall1gfp(+) microglia constituted the majority of phagocytes. A Sall1 deficiency did not affect microglial colonization of the retina and the cortex, but it did change their morphology from a ramified to a more amoeboid appearance. The morphological defects observed in Sall1-deficient microglia were not rescued by the presence of wild-type non-microglial cells, suggesting that Sall1 functions cell-autonomously in microglia. Taken together, our data indicate that Sall1 regulates microglial morphology during development. GLIA 2016;64:2005-2024.
authors.affiliation: Division of Molecular and Developmental Biology, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Koso
authors.affiliation: Division of Molecular and Developmental Biology, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Asano
authors.initials: A
authors.lastname: Tsuhako
authors.affiliation: Division of Stem Cell Processing and Stem Cell Bank, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Chen-Yi
authors.initials: CY
authors.lastname: Lai
authors.affiliation: Division of Molecular and Developmental Biology, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Baba
authors.affiliation: Division of Stem Cell Processing and Stem Cell Bank, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsu
authors.affiliation: Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Nagasaki
authors.affiliation: Department of Bioinformatics and Systems Biology, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Division of Molecular and Developmental Biology, Institute of Medical Science, the University of Tokyo, Tokyo, Japan. sumiko@ims.u-tokyo.ac.jp.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D056743:Cyclin D3 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D012162:Retinal Degeneration / Q000139:chemically induced / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C491049:Aif1 protein, mouse; D015703:Antigens, CD; D002135:Calcium-Binding Proteins; C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; C491297:MSI1 protein, human; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C472408:ROSA22 protein, mouse; C491254:Sall1 protein, mouse; D014157:Transcription Factors; D049452:Green Fluorescent Proteins
keywords: microglia; microglia development; neuroinflammation; retina; retinal degeneration