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HDAC3 But not HDAC2 Mediates Visual Experience-Dependent Radial Glia Proliferation in the Developing Xenopus Tectum

View Article: PubMed Central - PubMed

ABSTRACT

Radial glial cells (RGs) are one of the important progenitor cells that can differentiate into neurons or glia to form functional neural circuits in the developing central nervous system (CNS). Histone deacetylases (HDACs) has been associated with visual activity dependent changes in BrdU-positive progenitor cells in the developing brain. We previously have shown that HDAC1 is involved in the experience-dependent proliferation of RGs. However, it is less clear whether two other members of class I HDACs, HDAC2 and HDAC3, are involved in the regulation of radial glia proliferation. Here, we reported that HDAC2 and HDAC3 expression were developmentally regulated in tectal cells, especially in the ventricular layer of the BLBP-positive RGs. Pharmacological blockade using an inhibitor of class I HDACs, MS-275, decreased the number of BrdU-positive dividing progenitor cells. Specific knockdown of HDAC3 but not HDAC2 decreased the number of BrdU- and BLBP-labeled cells, suggesting that the proliferation of radial glia was selectively mediated by HDAC3. Visual deprivation induced selective augmentation of histone H4 acetylation at lysine 16 in BLBP-positive cells. Furthermore, the visual deprivation-induced increase in BrdU-positive cells was partially blocked by HDAC3 downregulation but not by HDAC2 knockdown at stage 49 tadpoles. These data revealed a specific role of HDAC3 in experience-dependent radial glia proliferation during the development of Xenopus tectum.

No MeSH data available.


Related in: MedlinePlus

BLBP+ radial glia are SOX2+ cells in the Xenopus tectum. (A) Optic tectum were co-labeled with anti-SOX2 and anti-BLBP antibodies at stage 48. Six representative sections of the whole tectum were shown (A1–A6: SOX2; A7-A12: BLBP; A13–A18: DAPI and A19–A24: SOX2 and BLBP merged). Arrow heads indicate the endfeet of Radial glial cells (RGs; A12, A25, and A26); Arrows indicate cells stained for DAPI and SOX2; Stars indicate the processes of radial glia; White circle indicates the cluster of SOX2+ cells (A3); White square indicates the area for counting the number of BrdU+ cells (A3). Stars indicate the elongated processes of RGs (A25-A26). Scale: 100 μm (zoom in: 20 μm). (B) Tadpoles were incubated with BrdU for 2 h and co-labeled with anti-BrdU and anti-BLBP antibodies at stage 47. Six representative sections were shown (B1–B6: BrdU staining; B7–B12: BLBP staining and B13–B18: BrdU and BLBP merged). White square (B5) indicates the area for the zoom in images (B19–B21). Scale: 100 μm (zoom in: 20 μm).
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Figure 1: BLBP+ radial glia are SOX2+ cells in the Xenopus tectum. (A) Optic tectum were co-labeled with anti-SOX2 and anti-BLBP antibodies at stage 48. Six representative sections of the whole tectum were shown (A1–A6: SOX2; A7-A12: BLBP; A13–A18: DAPI and A19–A24: SOX2 and BLBP merged). Arrow heads indicate the endfeet of Radial glial cells (RGs; A12, A25, and A26); Arrows indicate cells stained for DAPI and SOX2; Stars indicate the processes of radial glia; White circle indicates the cluster of SOX2+ cells (A3); White square indicates the area for counting the number of BrdU+ cells (A3). Stars indicate the elongated processes of RGs (A25-A26). Scale: 100 μm (zoom in: 20 μm). (B) Tadpoles were incubated with BrdU for 2 h and co-labeled with anti-BrdU and anti-BLBP antibodies at stage 47. Six representative sections were shown (B1–B6: BrdU staining; B7–B12: BLBP staining and B13–B18: BrdU and BLBP merged). White square (B5) indicates the area for the zoom in images (B19–B21). Scale: 100 μm (zoom in: 20 μm).

Mentions: To determine the location of neural progenitor cells (NPCs) in the optic tectum in vivo, we used an antibody of NPC marker sex-determining region Y-box 2 (SOX2) to immunostain the whole tectum at stage 48 (Figure 1A). Immunofluorescent images from the whole brain sections were scanned with a confocal microscope. We found that most SOX2-immuno positive (SOX2+) NPCs were present along the ventricle of the optic tectum (Figures 1A1–A6). A cluster of SOX2+ NPCs was distributed in the anterior forebrain of the optic tectum (Figure 1A3, circle). To determine whether SOX2+ cells are RGs, we immunostained the tectum with an anti-BLBP antibody, a well-characterized marker of RGs (Feng et al., 1994; D’Amico et al., 2011; Figures 1A7–A12). We observed that BLBP-labeled RGs have characteristic triangular cell bodies and single elongated processes with swollen endfeet that extended into the lateral neuropil (Figure 1A25). The BLBP+ RGs were only colocalized to those SOX2+ cell bodies which were distributed along the midline of the ventricle (Figure 1A26), indicating that RGs are NPCs at stage 48 tectum.


HDAC3 But not HDAC2 Mediates Visual Experience-Dependent Radial Glia Proliferation in the Developing Xenopus Tectum
BLBP+ radial glia are SOX2+ cells in the Xenopus tectum. (A) Optic tectum were co-labeled with anti-SOX2 and anti-BLBP antibodies at stage 48. Six representative sections of the whole tectum were shown (A1–A6: SOX2; A7-A12: BLBP; A13–A18: DAPI and A19–A24: SOX2 and BLBP merged). Arrow heads indicate the endfeet of Radial glial cells (RGs; A12, A25, and A26); Arrows indicate cells stained for DAPI and SOX2; Stars indicate the processes of radial glia; White circle indicates the cluster of SOX2+ cells (A3); White square indicates the area for counting the number of BrdU+ cells (A3). Stars indicate the elongated processes of RGs (A25-A26). Scale: 100 μm (zoom in: 20 μm). (B) Tadpoles were incubated with BrdU for 2 h and co-labeled with anti-BrdU and anti-BLBP antibodies at stage 47. Six representative sections were shown (B1–B6: BrdU staining; B7–B12: BLBP staining and B13–B18: BrdU and BLBP merged). White square (B5) indicates the area for the zoom in images (B19–B21). Scale: 100 μm (zoom in: 20 μm).
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5037170&req=5

Figure 1: BLBP+ radial glia are SOX2+ cells in the Xenopus tectum. (A) Optic tectum were co-labeled with anti-SOX2 and anti-BLBP antibodies at stage 48. Six representative sections of the whole tectum were shown (A1–A6: SOX2; A7-A12: BLBP; A13–A18: DAPI and A19–A24: SOX2 and BLBP merged). Arrow heads indicate the endfeet of Radial glial cells (RGs; A12, A25, and A26); Arrows indicate cells stained for DAPI and SOX2; Stars indicate the processes of radial glia; White circle indicates the cluster of SOX2+ cells (A3); White square indicates the area for counting the number of BrdU+ cells (A3). Stars indicate the elongated processes of RGs (A25-A26). Scale: 100 μm (zoom in: 20 μm). (B) Tadpoles were incubated with BrdU for 2 h and co-labeled with anti-BrdU and anti-BLBP antibodies at stage 47. Six representative sections were shown (B1–B6: BrdU staining; B7–B12: BLBP staining and B13–B18: BrdU and BLBP merged). White square (B5) indicates the area for the zoom in images (B19–B21). Scale: 100 μm (zoom in: 20 μm).
Mentions: To determine the location of neural progenitor cells (NPCs) in the optic tectum in vivo, we used an antibody of NPC marker sex-determining region Y-box 2 (SOX2) to immunostain the whole tectum at stage 48 (Figure 1A). Immunofluorescent images from the whole brain sections were scanned with a confocal microscope. We found that most SOX2-immuno positive (SOX2+) NPCs were present along the ventricle of the optic tectum (Figures 1A1–A6). A cluster of SOX2+ NPCs was distributed in the anterior forebrain of the optic tectum (Figure 1A3, circle). To determine whether SOX2+ cells are RGs, we immunostained the tectum with an anti-BLBP antibody, a well-characterized marker of RGs (Feng et al., 1994; D’Amico et al., 2011; Figures 1A7–A12). We observed that BLBP-labeled RGs have characteristic triangular cell bodies and single elongated processes with swollen endfeet that extended into the lateral neuropil (Figure 1A25). The BLBP+ RGs were only colocalized to those SOX2+ cell bodies which were distributed along the midline of the ventricle (Figure 1A26), indicating that RGs are NPCs at stage 48 tectum.

View Article: PubMed Central - PubMed

ABSTRACT

Radial glial cells (RGs) are one of the important progenitor cells that can differentiate into neurons or glia to form functional neural circuits in the developing central nervous system (CNS). Histone deacetylases (HDACs) has been associated with visual activity dependent changes in BrdU-positive progenitor cells in the developing brain. We previously have shown that HDAC1 is involved in the experience-dependent proliferation of RGs. However, it is less clear whether two other members of class I HDACs, HDAC2 and HDAC3, are involved in the regulation of radial glia proliferation. Here, we reported that HDAC2 and HDAC3 expression were developmentally regulated in tectal cells, especially in the ventricular layer of the BLBP-positive RGs. Pharmacological blockade using an inhibitor of class I HDACs, MS-275, decreased the number of BrdU-positive dividing progenitor cells. Specific knockdown of HDAC3 but not HDAC2 decreased the number of BrdU- and BLBP-labeled cells, suggesting that the proliferation of radial glia was selectively mediated by HDAC3. Visual deprivation induced selective augmentation of histone H4 acetylation at lysine 16 in BLBP-positive cells. Furthermore, the visual deprivation-induced increase in BrdU-positive cells was partially blocked by HDAC3 downregulation but not by HDAC2 knockdown at stage 49 tadpoles. These data revealed a specific role of HDAC3 in experience-dependent radial glia proliferation during the development of Xenopus tectum.

No MeSH data available.


Related in: MedlinePlus