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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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Double labeling of GABAergic interneuron precursors with the cell-division marker Ki67. Ki67 immunofluorescence (red) was observed in many cell nuclei throughout the proliferative layers of the neocortex. This coincided with expression of the transcription factors ASCL1 and DLX2 (green) and a majority of cells appeared double labeled for Ki67 and either one of the transcription factors (yellow, 9A,B). DLX2 was less widely expressed than ASCL1, being largely confined to the ISVZ (B). CALB2 was also widely expressed in the SVZ (green, C) but was not seen to be co-expressed with Ki67. Scale bar = 100 μm.
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BHT254F9: Double labeling of GABAergic interneuron precursors with the cell-division marker Ki67. Ki67 immunofluorescence (red) was observed in many cell nuclei throughout the proliferative layers of the neocortex. This coincided with expression of the transcription factors ASCL1 and DLX2 (green) and a majority of cells appeared double labeled for Ki67 and either one of the transcription factors (yellow, 9A,B). DLX2 was less widely expressed than ASCL1, being largely confined to the ISVZ (B). CALB2 was also widely expressed in the SVZ (green, C) but was not seen to be co-expressed with Ki67. Scale bar = 100 μm.

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)

Double labeling of GABAergic interneuron precursors with the cell-division marker Ki67. Ki67 immunofluorescence (red) was observed in many cell nuclei throughout the proliferative layers of the neocortex. This coincided with expression of the transcription factors ASCL1 and DLX2 (green) and a majority of cells appeared double labeled for Ki67 and either one of the transcription factors (yellow, 9A,B). DLX2 was less widely expressed than ASCL1, being largely confined to the ISVZ (B). CALB2 was also widely expressed in the SVZ (green, C) but was not seen to be co-expressed with Ki67. Scale bar = 100 μm.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

BHT254F9: Double labeling of GABAergic interneuron precursors with the cell-division marker Ki67. Ki67 immunofluorescence (red) was observed in many cell nuclei throughout the proliferative layers of the neocortex. This coincided with expression of the transcription factors ASCL1 and DLX2 (green) and a majority of cells appeared double labeled for Ki67 and either one of the transcription factors (yellow, 9A,B). DLX2 was less widely expressed than ASCL1, being largely confined to the ISVZ (B). CALB2 was also widely expressed in the SVZ (green, C) but was not seen to be co-expressed with Ki67. Scale bar = 100 μm.
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