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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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Expression gradients for immunoreactivity to GABAergic markers confirmed by optical densitometry. IHC for four proteins was selected for measurement at multiple ages; DLX2 (A), ASCL1 (B), GAD2 (C), and CALB2 (D). Low power images of immunostaining for each protein are shown, all at 9 PCW in medial sagittal sections. DLX2, ASCL1, and GAD2 all show moderate immunoreactivity in the medial ganglionic eminence but stronger expression in the neocortex, especially in the cortical plate (CP) but also in the ventricular and subventricular zone (VZ/SVZ) and a gradient of expression from the anterior to posterior pole of the neocortex. CALB2 also shows a gradient of expression, but differs from the other 3 in showing moderate expression in fibers in the subplate and intermediate zone (SP/IZ) but low expression in VZ/SVZ and the MGE. The ratio of anterior to posterior labeling density was calculated for each section and the mean plotted. Error bars represent 95% confidence limits of the mean, which are sometimes close enough together to be obscured by the representative symbol. With the exception of DLX2 expression at 8 PCW, there was consistently higher expression anteriorly for all genes and time point studied. The prethalamus (PrTh) and thalamus (Th) show low immunoreactivity for all four markers, with the exception of CALB2 expression in the thalamus. Scale bar = 2 mm. The orientation of all the section images is the same, hence Ant and Pos are the same as indicated in A.
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BHT254F4: Expression gradients for immunoreactivity to GABAergic markers confirmed by optical densitometry. IHC for four proteins was selected for measurement at multiple ages; DLX2 (A), ASCL1 (B), GAD2 (C), and CALB2 (D). Low power images of immunostaining for each protein are shown, all at 9 PCW in medial sagittal sections. DLX2, ASCL1, and GAD2 all show moderate immunoreactivity in the medial ganglionic eminence but stronger expression in the neocortex, especially in the cortical plate (CP) but also in the ventricular and subventricular zone (VZ/SVZ) and a gradient of expression from the anterior to posterior pole of the neocortex. CALB2 also shows a gradient of expression, but differs from the other 3 in showing moderate expression in fibers in the subplate and intermediate zone (SP/IZ) but low expression in VZ/SVZ and the MGE. The ratio of anterior to posterior labeling density was calculated for each section and the mean plotted. Error bars represent 95% confidence limits of the mean, which are sometimes close enough together to be obscured by the representative symbol. With the exception of DLX2 expression at 8 PCW, there was consistently higher expression anteriorly for all genes and time point studied. The prethalamus (PrTh) and thalamus (Th) show low immunoreactivity for all four markers, with the exception of CALB2 expression in the thalamus. Scale bar = 2 mm. The orientation of all the section images is the same, hence Ant and Pos are the same as indicated in A.

Mentions: Whole sagittal sections of fetal brain were also successfully immunostained for 4 markers of GABAergic interneurons, DLX2, ASCL1, GAD2, and CALB2 between 8 and 12 PCW weeks. At all stages, a similar expression pattern was observed for DLX2, ASCL1, and GAD2, with moderate expression in the GE, but stronger expression in the CP (Fig. 4). There was also some expression in the VZ/SVZ when compared with areas of completely negative staining in the diencephalon. CALB2 showed a different pattern of staining. CALB2-positive neurons were present in the postmitotic layers of the lateral (Fig. 5B,C) and caudal (not shown) GE, but were absent from the MGE (Fig. 4D). In the cortex, CALB2-positive neuronal cell bodies were prominent in the cortical plate (CP) at 8–9 PCW, with fewer also present in the marginal zone and subplate, but with many immunoreactive fibers present in the subplate and intermediate zone (Figs 4D and 5B). No immunostaining was present in the proliferative zones at these earlier stages.Figure 4.


The early fetal development of human neocortical GABAergic interneurons.

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

Expression gradients for immunoreactivity to GABAergic markers confirmed by optical densitometry. IHC for four proteins was selected for measurement at multiple ages; DLX2 (A), ASCL1 (B), GAD2 (C), and CALB2 (D). Low power images of immunostaining for each protein are shown, all at 9 PCW in medial sagittal sections. DLX2, ASCL1, and GAD2 all show moderate immunoreactivity in the medial ganglionic eminence but stronger expression in the neocortex, especially in the cortical plate (CP) but also in the ventricular and subventricular zone (VZ/SVZ) and a gradient of expression from the anterior to posterior pole of the neocortex. CALB2 also shows a gradient of expression, but differs from the other 3 in showing moderate expression in fibers in the subplate and intermediate zone (SP/IZ) but low expression in VZ/SVZ and the MGE. The ratio of anterior to posterior labeling density was calculated for each section and the mean plotted. Error bars represent 95% confidence limits of the mean, which are sometimes close enough together to be obscured by the representative symbol. With the exception of DLX2 expression at 8 PCW, there was consistently higher expression anteriorly for all genes and time point studied. The prethalamus (PrTh) and thalamus (Th) show low immunoreactivity for all four markers, with the exception of CALB2 expression in the thalamus. Scale bar = 2 mm. The orientation of all the section images is the same, hence Ant and Pos are the same as indicated in A.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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BHT254F4: Expression gradients for immunoreactivity to GABAergic markers confirmed by optical densitometry. IHC for four proteins was selected for measurement at multiple ages; DLX2 (A), ASCL1 (B), GAD2 (C), and CALB2 (D). Low power images of immunostaining for each protein are shown, all at 9 PCW in medial sagittal sections. DLX2, ASCL1, and GAD2 all show moderate immunoreactivity in the medial ganglionic eminence but stronger expression in the neocortex, especially in the cortical plate (CP) but also in the ventricular and subventricular zone (VZ/SVZ) and a gradient of expression from the anterior to posterior pole of the neocortex. CALB2 also shows a gradient of expression, but differs from the other 3 in showing moderate expression in fibers in the subplate and intermediate zone (SP/IZ) but low expression in VZ/SVZ and the MGE. The ratio of anterior to posterior labeling density was calculated for each section and the mean plotted. Error bars represent 95% confidence limits of the mean, which are sometimes close enough together to be obscured by the representative symbol. With the exception of DLX2 expression at 8 PCW, there was consistently higher expression anteriorly for all genes and time point studied. The prethalamus (PrTh) and thalamus (Th) show low immunoreactivity for all four markers, with the exception of CALB2 expression in the thalamus. Scale bar = 2 mm. The orientation of all the section images is the same, hence Ant and Pos are the same as indicated in A.
Mentions: Whole sagittal sections of fetal brain were also successfully immunostained for 4 markers of GABAergic interneurons, DLX2, ASCL1, GAD2, and CALB2 between 8 and 12 PCW weeks. At all stages, a similar expression pattern was observed for DLX2, ASCL1, and GAD2, with moderate expression in the GE, but stronger expression in the CP (Fig. 4). There was also some expression in the VZ/SVZ when compared with areas of completely negative staining in the diencephalon. CALB2 showed a different pattern of staining. CALB2-positive neurons were present in the postmitotic layers of the lateral (Fig. 5B,C) and caudal (not shown) GE, but were absent from the MGE (Fig. 4D). In the cortex, CALB2-positive neuronal cell bodies were prominent in the cortical plate (CP) at 8–9 PCW, with fewer also present in the marginal zone and subplate, but with many immunoreactive fibers present in the subplate and intermediate zone (Figs 4D and 5B). No immunostaining was present in the proliferative zones at these earlier stages.Figure 4.

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