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NG2 glia are required for vessel network formation during embryonic development.

Minocha S, Valloton D, Brunet I, Eichmann A, Hornung JP, Lebrand C - Elife (2015)

Bottom Line: Interestingly, their appearance temporally coincides with the establishment of blood vessel network in the embryonic brain.NG2(+) glia are closely apposed to developing cerebral vessels by being either positioned at the sprouting tip cells or tethered along the vessel walls.By revealing a novel and fundamental role for NG2(+) glia, our study brings new perspectives to mechanisms underlying proper vessels network formation in embryonic brains.

View Article: PubMed Central - PubMed

Affiliation: Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.

ABSTRACT
The NG2(+) glia, also known as polydendrocytes or oligodendrocyte precursor cells, represent a new entity among glial cell populations in the central nervous system. However, the complete repertoire of their roles is not yet identified. The embryonic NG2(+) glia originate from the Nkx2.1(+) progenitors of the ventral telencephalon. Our analysis unravels that, beginning from E12.5 until E16.5, the NG2(+) glia populate the entire dorsal telencephalon. Interestingly, their appearance temporally coincides with the establishment of blood vessel network in the embryonic brain. NG2(+) glia are closely apposed to developing cerebral vessels by being either positioned at the sprouting tip cells or tethered along the vessel walls. Absence of NG2(+) glia drastically affects the vascular development leading to severe reduction of ramifications and connections by E18.5. By revealing a novel and fundamental role for NG2(+) glia, our study brings new perspectives to mechanisms underlying proper vessels network formation in embryonic brains.

No MeSH data available.


Related in: MedlinePlus

Nkx2.1-derived NG2 and Olig2 glia are transient and gradually disappear from the dorsal pallium at postnatal ages.(A–C) Double immunohistochemistry for GFP and NG2 on coronal telencephalicsections from Nkx2.1-cre+/Rosa-EYFP mice at P0 (n=3) (A1–A2), P2 (n=3) (B1–B2), and P8 (n=2) (C1–C2). (D) Double immunohistochemistry for GFP and Olig2 on coronal telencephalicsections from Nkx2.1-cre+/Rosa-EYFP mice at P8 (n=2) (D1–D3). Cell nuclei were counterstained in blue with Hoechst (A1, B1, and C1). A2, B2, C2, and D3 are high-power views of the cingulate bundle (Cl) seen in A1, B1, C1, and D1, respectively. In the Cl of Nkx2.1-cre+/Rosa-EYFP mice brains at P2, only very few Nkx2.1-derived NG2 glia remained (arrowheads B2). At P8, Nkx2.1-derived NG2 and Olig2 glia disappeared completely and were replaced by NG2 and Olig2 glia that did not expressed the YFP and were not derived from Nkx2.1 germinal domains (open arrowheads in A2 and C2). At all postnatal ages many Nkx2.1-derived GABAergic interneurons found in this region were not labeled for NG2 (arrows in B2 and C2).Scale bar = 675 µm in A1, B1, C1 and D1; 40 µm in A2, B2 and C2; 100 µm in D2 and D3. CC, corpus callosum; CCi, cingulate cortex; LV, lateral ventricles; SEP, septum.DOI:http://dx.doi.org/10.7554/eLife.09102.006
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fig2s2: Nkx2.1-derived NG2 and Olig2 glia are transient and gradually disappear from the dorsal pallium at postnatal ages.(A–C) Double immunohistochemistry for GFP and NG2 on coronal telencephalicsections from Nkx2.1-cre+/Rosa-EYFP mice at P0 (n=3) (A1–A2), P2 (n=3) (B1–B2), and P8 (n=2) (C1–C2). (D) Double immunohistochemistry for GFP and Olig2 on coronal telencephalicsections from Nkx2.1-cre+/Rosa-EYFP mice at P8 (n=2) (D1–D3). Cell nuclei were counterstained in blue with Hoechst (A1, B1, and C1). A2, B2, C2, and D3 are high-power views of the cingulate bundle (Cl) seen in A1, B1, C1, and D1, respectively. In the Cl of Nkx2.1-cre+/Rosa-EYFP mice brains at P2, only very few Nkx2.1-derived NG2 glia remained (arrowheads B2). At P8, Nkx2.1-derived NG2 and Olig2 glia disappeared completely and were replaced by NG2 and Olig2 glia that did not expressed the YFP and were not derived from Nkx2.1 germinal domains (open arrowheads in A2 and C2). At all postnatal ages many Nkx2.1-derived GABAergic interneurons found in this region were not labeled for NG2 (arrows in B2 and C2).Scale bar = 675 µm in A1, B1, C1 and D1; 40 µm in A2, B2 and C2; 100 µm in D2 and D3. CC, corpus callosum; CCi, cingulate cortex; LV, lateral ventricles; SEP, septum.DOI:http://dx.doi.org/10.7554/eLife.09102.006

Mentions: As Nkx2.1-regulated precursors have been previously shown in embryos to produce transient oligodendrocyte precursor cells (OPCs) in addition to giving rise to GABAergic interneurons and astrocytes (Nery et al., 2001; Kessaris et al., 2006, Minocha et al., 2015), we decided to make use of the Nkx2.1-cre+/Rosa-EYFP mice to look further at the subpallial origin, time of appearance and spatial arrangement of the embryonic NG2+ glia that ubiquitously occupied the dorsal telencephalon toward the end of embryonic development. Using our Nkx2.1-cre+/Rosa-EYFP mice, our findings confirmed that Nkx2.1-derived precursors produced YFP+/NG2+ glia that colonized the cingulate cortical area and the midline (Figure 2F, Figure 2—figure supplement 1F) (Kessaris et al., 2006). The YFP signal was detected in all embryonic NG2+ glia of the dorsal telencephalon from E16.5 to E18.5 (100% colocalization in the CC, and the CCi at E16.5 and E18.5; n=5) (Figure 2F). Nkx2.1-derived NG2+ glia expressed Olig2 (n=5) and S100β (n=4) (Figure 2G–H), and lacked GLAST (n=4) or GFAP (n=3) expression (Figure 2I–J). This further emphasized that subpallial domains are sites for early NG2+ glia genesis. Furthermore, we followed the presence of these YFP+ /NG2+ glia after birth. We observed that the YFP+/Olig2+/NG2+ glia originating from Nkx2.1 domains were transient in nature and disappeared abruptly from the cortex around P8 (n=3) (Figure 2—figure supplement 2). These results are coherent with previous studies, wherein the OPCs generated from the Nkx2.1-expressing precursors were shown to disappear around P10 (Kessaris et al., 2006). Interestingly, we never detected any YFP signal in the ECs and the pericytes of the cerebral vasculature (Figure 3A1 and 3C ; n=5). Thus, based on the specificity of the Cre- reporter strains (both Cspg4-cre and Nkx2.1-cre) for NG2+ glia, these mice can be further utilized to determine the function of the embryonic NG2+ glia independent of ECs and pericytes.


NG2 glia are required for vessel network formation during embryonic development.

Minocha S, Valloton D, Brunet I, Eichmann A, Hornung JP, Lebrand C - Elife (2015)

Nkx2.1-derived NG2 and Olig2 glia are transient and gradually disappear from the dorsal pallium at postnatal ages.(A–C) Double immunohistochemistry for GFP and NG2 on coronal telencephalicsections from Nkx2.1-cre+/Rosa-EYFP mice at P0 (n=3) (A1–A2), P2 (n=3) (B1–B2), and P8 (n=2) (C1–C2). (D) Double immunohistochemistry for GFP and Olig2 on coronal telencephalicsections from Nkx2.1-cre+/Rosa-EYFP mice at P8 (n=2) (D1–D3). Cell nuclei were counterstained in blue with Hoechst (A1, B1, and C1). A2, B2, C2, and D3 are high-power views of the cingulate bundle (Cl) seen in A1, B1, C1, and D1, respectively. In the Cl of Nkx2.1-cre+/Rosa-EYFP mice brains at P2, only very few Nkx2.1-derived NG2 glia remained (arrowheads B2). At P8, Nkx2.1-derived NG2 and Olig2 glia disappeared completely and were replaced by NG2 and Olig2 glia that did not expressed the YFP and were not derived from Nkx2.1 germinal domains (open arrowheads in A2 and C2). At all postnatal ages many Nkx2.1-derived GABAergic interneurons found in this region were not labeled for NG2 (arrows in B2 and C2).Scale bar = 675 µm in A1, B1, C1 and D1; 40 µm in A2, B2 and C2; 100 µm in D2 and D3. CC, corpus callosum; CCi, cingulate cortex; LV, lateral ventricles; SEP, septum.DOI:http://dx.doi.org/10.7554/eLife.09102.006
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fig2s2: Nkx2.1-derived NG2 and Olig2 glia are transient and gradually disappear from the dorsal pallium at postnatal ages.(A–C) Double immunohistochemistry for GFP and NG2 on coronal telencephalicsections from Nkx2.1-cre+/Rosa-EYFP mice at P0 (n=3) (A1–A2), P2 (n=3) (B1–B2), and P8 (n=2) (C1–C2). (D) Double immunohistochemistry for GFP and Olig2 on coronal telencephalicsections from Nkx2.1-cre+/Rosa-EYFP mice at P8 (n=2) (D1–D3). Cell nuclei were counterstained in blue with Hoechst (A1, B1, and C1). A2, B2, C2, and D3 are high-power views of the cingulate bundle (Cl) seen in A1, B1, C1, and D1, respectively. In the Cl of Nkx2.1-cre+/Rosa-EYFP mice brains at P2, only very few Nkx2.1-derived NG2 glia remained (arrowheads B2). At P8, Nkx2.1-derived NG2 and Olig2 glia disappeared completely and were replaced by NG2 and Olig2 glia that did not expressed the YFP and were not derived from Nkx2.1 germinal domains (open arrowheads in A2 and C2). At all postnatal ages many Nkx2.1-derived GABAergic interneurons found in this region were not labeled for NG2 (arrows in B2 and C2).Scale bar = 675 µm in A1, B1, C1 and D1; 40 µm in A2, B2 and C2; 100 µm in D2 and D3. CC, corpus callosum; CCi, cingulate cortex; LV, lateral ventricles; SEP, septum.DOI:http://dx.doi.org/10.7554/eLife.09102.006
Mentions: As Nkx2.1-regulated precursors have been previously shown in embryos to produce transient oligodendrocyte precursor cells (OPCs) in addition to giving rise to GABAergic interneurons and astrocytes (Nery et al., 2001; Kessaris et al., 2006, Minocha et al., 2015), we decided to make use of the Nkx2.1-cre+/Rosa-EYFP mice to look further at the subpallial origin, time of appearance and spatial arrangement of the embryonic NG2+ glia that ubiquitously occupied the dorsal telencephalon toward the end of embryonic development. Using our Nkx2.1-cre+/Rosa-EYFP mice, our findings confirmed that Nkx2.1-derived precursors produced YFP+/NG2+ glia that colonized the cingulate cortical area and the midline (Figure 2F, Figure 2—figure supplement 1F) (Kessaris et al., 2006). The YFP signal was detected in all embryonic NG2+ glia of the dorsal telencephalon from E16.5 to E18.5 (100% colocalization in the CC, and the CCi at E16.5 and E18.5; n=5) (Figure 2F). Nkx2.1-derived NG2+ glia expressed Olig2 (n=5) and S100β (n=4) (Figure 2G–H), and lacked GLAST (n=4) or GFAP (n=3) expression (Figure 2I–J). This further emphasized that subpallial domains are sites for early NG2+ glia genesis. Furthermore, we followed the presence of these YFP+ /NG2+ glia after birth. We observed that the YFP+/Olig2+/NG2+ glia originating from Nkx2.1 domains were transient in nature and disappeared abruptly from the cortex around P8 (n=3) (Figure 2—figure supplement 2). These results are coherent with previous studies, wherein the OPCs generated from the Nkx2.1-expressing precursors were shown to disappear around P10 (Kessaris et al., 2006). Interestingly, we never detected any YFP signal in the ECs and the pericytes of the cerebral vasculature (Figure 3A1 and 3C ; n=5). Thus, based on the specificity of the Cre- reporter strains (both Cspg4-cre and Nkx2.1-cre) for NG2+ glia, these mice can be further utilized to determine the function of the embryonic NG2+ glia independent of ECs and pericytes.

Bottom Line: Interestingly, their appearance temporally coincides with the establishment of blood vessel network in the embryonic brain.NG2(+) glia are closely apposed to developing cerebral vessels by being either positioned at the sprouting tip cells or tethered along the vessel walls.By revealing a novel and fundamental role for NG2(+) glia, our study brings new perspectives to mechanisms underlying proper vessels network formation in embryonic brains.

View Article: PubMed Central - PubMed

Affiliation: Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.

ABSTRACT
The NG2(+) glia, also known as polydendrocytes or oligodendrocyte precursor cells, represent a new entity among glial cell populations in the central nervous system. However, the complete repertoire of their roles is not yet identified. The embryonic NG2(+) glia originate from the Nkx2.1(+) progenitors of the ventral telencephalon. Our analysis unravels that, beginning from E12.5 until E16.5, the NG2(+) glia populate the entire dorsal telencephalon. Interestingly, their appearance temporally coincides with the establishment of blood vessel network in the embryonic brain. NG2(+) glia are closely apposed to developing cerebral vessels by being either positioned at the sprouting tip cells or tethered along the vessel walls. Absence of NG2(+) glia drastically affects the vascular development leading to severe reduction of ramifications and connections by E18.5. By revealing a novel and fundamental role for NG2(+) glia, our study brings new perspectives to mechanisms underlying proper vessels network formation in embryonic brains.

No MeSH data available.


Related in: MedlinePlus