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The early fetal development of human neocortical GABAergic interneurons.

Al-Jaberi N, Lindsay S, Sarma S, Bayatti N, Clowry GJ - Cereb. Cortex (2013)

Bottom Line: CALB2-positive cells increased steadily in the SVZ/VZ from 10 PCW but were not double-labeled with Ki-67.Expression of GABAergic genes was generally higher in the dorsal pallium than in the ganglionic eminences, with lower expression in the intervening ventral pallium.It is widely accepted that the cortical proliferative zones may generate CALB2-positive interneurons from mid-gestation; we now show that the anterior neocortical proliferative layers especially may be a rich source of interneurons in the early neocortex.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.

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Laminar expression of GABAergic genes at 12 PCW. Panel (A) shows at low magnification the expression of GAD1 and DLX2 by ISH, and DLX2 and CALB2 by IHC. GAD1 expression indicated the presence of GABAergic neurons in the cortical plate at this stage, and the expression of DLX2/DLX2 in the proliferative zones suggests that GABAergic cells may have been generated intracortically at this stage. This stage of development is noticeable for the appearance of CALB2 immunoreactive neurons in the VZ, SVZ, and intermediate zones. At higher magnification (B), many of these CALB2-positive cells appeared migratory, but have a mix of orientations suggestive of tangential or radial migration. Note that the marginal zone (MZ) has a cell-containing outer layer (subpial granular layer) at this age. Scale bar = 500 μm in A; 100 μm in B.
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BHT254F8: Laminar expression of GABAergic genes at 12 PCW. Panel (A) shows at low magnification the expression of GAD1 and DLX2 by ISH, and DLX2 and CALB2 by IHC. GAD1 expression indicated the presence of GABAergic neurons in the cortical plate at this stage, and the expression of DLX2/DLX2 in the proliferative zones suggests that GABAergic cells may have been generated intracortically at this stage. This stage of development is noticeable for the appearance of CALB2 immunoreactive neurons in the VZ, SVZ, and intermediate zones. At higher magnification (B), many of these CALB2-positive cells appeared migratory, but have a mix of orientations suggestive of tangential or radial migration. Note that the marginal zone (MZ) has a cell-containing outer layer (subpial granular layer) at this age. Scale bar = 500 μm in A; 100 μm in B.

Mentions: By 12 PCW, as previously described (Bayatti, Moss et al. 2008), CALB2-positive neurons were now observed in the proliferative zones and intermediate zone, particularly at the anterior pole (Fig. 8). Many of these cells were of bipolar appearance, suggesting they are migratory cells. There was a mixture of radially and tangentially orientated cells, and alignments in between (Fig. 8B). At this stage, other GABAergic genes were also expressed, including GAD1 and DLX2 detected by ISH (Fig. 8A) and also DLX2 by IHC. In each case, expression was prominent in the upper CP and outer SVZ (OSVZ). DLX2 immunoreactivity was also prominent in the inner SVZ (ISVZ) but not the VZ, whereas DLX2 mRNA expression was observed in the VZ (Fig. 8A). In order to confirm the expression of GABAergic markers in proliferating cells in the cortical wall, double immunofluorescent staining was carried out for the cell division marker Ki67 (Brown and Gatter 1990; Zecevic et al. 2011) and either ASCL1, DLX2, or CALB2 (Fig. 9). All 4 proteins were detected in the VZ and SVZ at 11 PCW, although DLX2 positive cells were mostly confined to the ISVZ. Only ASCL1 and DLX2 showed extensive double-labeling with Ki67; no CALB2 positive cells were found to be also Ki67 positive.Figure 8.


The early fetal development of human neocortical GABAergic interneurons.

Al-Jaberi N, Lindsay S, Sarma S, Bayatti N, Clowry GJ - Cereb. Cortex (2013)

Laminar expression of GABAergic genes at 12 PCW. Panel (A) shows at low magnification the expression of GAD1 and DLX2 by ISH, and DLX2 and CALB2 by IHC. GAD1 expression indicated the presence of GABAergic neurons in the cortical plate at this stage, and the expression of DLX2/DLX2 in the proliferative zones suggests that GABAergic cells may have been generated intracortically at this stage. This stage of development is noticeable for the appearance of CALB2 immunoreactive neurons in the VZ, SVZ, and intermediate zones. At higher magnification (B), many of these CALB2-positive cells appeared migratory, but have a mix of orientations suggestive of tangential or radial migration. Note that the marginal zone (MZ) has a cell-containing outer layer (subpial granular layer) at this age. Scale bar = 500 μm in A; 100 μm in B.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4318531&req=5

BHT254F8: Laminar expression of GABAergic genes at 12 PCW. Panel (A) shows at low magnification the expression of GAD1 and DLX2 by ISH, and DLX2 and CALB2 by IHC. GAD1 expression indicated the presence of GABAergic neurons in the cortical plate at this stage, and the expression of DLX2/DLX2 in the proliferative zones suggests that GABAergic cells may have been generated intracortically at this stage. This stage of development is noticeable for the appearance of CALB2 immunoreactive neurons in the VZ, SVZ, and intermediate zones. At higher magnification (B), many of these CALB2-positive cells appeared migratory, but have a mix of orientations suggestive of tangential or radial migration. Note that the marginal zone (MZ) has a cell-containing outer layer (subpial granular layer) at this age. Scale bar = 500 μm in A; 100 μm in B.
Mentions: By 12 PCW, as previously described (Bayatti, Moss et al. 2008), CALB2-positive neurons were now observed in the proliferative zones and intermediate zone, particularly at the anterior pole (Fig. 8). Many of these cells were of bipolar appearance, suggesting they are migratory cells. There was a mixture of radially and tangentially orientated cells, and alignments in between (Fig. 8B). At this stage, other GABAergic genes were also expressed, including GAD1 and DLX2 detected by ISH (Fig. 8A) and also DLX2 by IHC. In each case, expression was prominent in the upper CP and outer SVZ (OSVZ). DLX2 immunoreactivity was also prominent in the inner SVZ (ISVZ) but not the VZ, whereas DLX2 mRNA expression was observed in the VZ (Fig. 8A). In order to confirm the expression of GABAergic markers in proliferating cells in the cortical wall, double immunofluorescent staining was carried out for the cell division marker Ki67 (Brown and Gatter 1990; Zecevic et al. 2011) and either ASCL1, DLX2, or CALB2 (Fig. 9). All 4 proteins were detected in the VZ and SVZ at 11 PCW, although DLX2 positive cells were mostly confined to the ISVZ. Only ASCL1 and DLX2 showed extensive double-labeling with Ki67; no CALB2 positive cells were found to be also Ki67 positive.Figure 8.

Bottom Line: CALB2-positive cells increased steadily in the SVZ/VZ from 10 PCW but were not double-labeled with Ki-67.Expression of GABAergic genes was generally higher in the dorsal pallium than in the ganglionic eminences, with lower expression in the intervening ventral pallium.It is widely accepted that the cortical proliferative zones may generate CALB2-positive interneurons from mid-gestation; we now show that the anterior neocortical proliferative layers especially may be a rich source of interneurons in the early neocortex.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.

Show MeSH
Related in: MedlinePlus