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Diversity of cortical interneurons in primates: the role of the dorsal proliferative niche.

Radonjić NV, Ayoub AE, Memi F, Yu X, Maroof A, Jakovcevski I, Anderson SA, Rakic P, Zecevic N - Cell Rep (2014)

Bottom Line: For example, GABAergic interneurons of the mammalian neocortex are generated in the ventral telencephalon and migrate tangentially to the neocortex, in contrast to the projection neurons originating in the ventricular/subventricular zone (VZ/SVZ) of the dorsal telencephalon.The origin, magnitude, and significance of this species-specific difference are not known.Our findings suggest that these progenitors constitute an evolutionary novelty contributing to the elaboration of higher cognitive functions in primates.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA; Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Pasterova 2, 11000 Belgrade, Serbia.

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The Expression of Nkx2.1 Transcription Factor in the Human Forebrain(A–C) Drawing of a coronal section of a 20 GW forebrain with distribution pattern of immunolabeled Nkx2.1+ cells. (B) MGE and cortical VZ/SVZ. (C) In situ (FISH) signal for mRNA Nkx2.1 (red) in the whole cerebral cortex at midterm.(D) In situ hybridization (red) and immunolabeling with Nkx2.1 antibody (green) show colocalization of mRNA and protein.(E and F) (E) mRNA Nkx2.1 (red) and Gad67 immunolabeling (green) in the same cells; (F) mRNA Gad67 (red) and Nkx2.1 immunolabeling (green) in the same cells. (G) Graphs demonstrating the percentage of Nkx2.1+ cells from total number of cells in three gestational ages (15, 18–19, and 22 GW) and two regions: ventricular zone (VZ) and subventricular zone (SVZ).(H) RT-PCR of human cortical tissue for Nkx2.1 and Lhx6 in three stages: 16, 18, and 19 GW; y axis, values represent fold increase normalized to 16 GW values.(I) Western blot for transcription factors at 18 GW in the cortex (Cx) and ganglionic eminence (GE).CP, cortical plate; VZ, ventricular zone; SVZ, subventricular zone. Scale bars represent 200 μm (B) and 50 μm (C–F) 50μm; insets in (D–F) represent 10 μm.
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Figure 1: The Expression of Nkx2.1 Transcription Factor in the Human Forebrain(A–C) Drawing of a coronal section of a 20 GW forebrain with distribution pattern of immunolabeled Nkx2.1+ cells. (B) MGE and cortical VZ/SVZ. (C) In situ (FISH) signal for mRNA Nkx2.1 (red) in the whole cerebral cortex at midterm.(D) In situ hybridization (red) and immunolabeling with Nkx2.1 antibody (green) show colocalization of mRNA and protein.(E and F) (E) mRNA Nkx2.1 (red) and Gad67 immunolabeling (green) in the same cells; (F) mRNA Gad67 (red) and Nkx2.1 immunolabeling (green) in the same cells. (G) Graphs demonstrating the percentage of Nkx2.1+ cells from total number of cells in three gestational ages (15, 18–19, and 22 GW) and two regions: ventricular zone (VZ) and subventricular zone (SVZ).(H) RT-PCR of human cortical tissue for Nkx2.1 and Lhx6 in three stages: 16, 18, and 19 GW; y axis, values represent fold increase normalized to 16 GW values.(I) Western blot for transcription factors at 18 GW in the cortex (Cx) and ganglionic eminence (GE).CP, cortical plate; VZ, ventricular zone; SVZ, subventricular zone. Scale bars represent 200 μm (B) and 50 μm (C–F) 50μm; insets in (D–F) represent 10 μm.

Mentions: To analyze Nkx2.1 gene expression in the cerebral cortex, we studied human and macaque monkey fetal forebrain tissue at the comparable midgestational stages. We found out that Nkx2.1 was expressed in a decreasing gradient, from high in the medial ganglionic eminence (MGE) to low in the cortical wall, on coronal sections cut through the middle of the telencephalon (Figures 1A–1C). We quantified immunolabeled Nkx2.1+ cells (15–22 gestational weeks [GW]; n = 6). In particular, a higher percentage of Nkx2.1+ cells was observed in the cortical SVZ compared to the VZ (Figure 1G). At 15 GW, 4.2% and 9% of cells were Nkx2.1+ in the VZ and SVZ, respectively; at 18–19 GW, 4.9% and 7.8%; and at 22 GW, 2.6% and 6.4% (Figure 1G). These values probably underestimate the real number of cortical Nkx2.1+ cells, since we applied restrictive counting criteria including only cells with the brightest signal.


Diversity of cortical interneurons in primates: the role of the dorsal proliferative niche.

Radonjić NV, Ayoub AE, Memi F, Yu X, Maroof A, Jakovcevski I, Anderson SA, Rakic P, Zecevic N - Cell Rep (2014)

The Expression of Nkx2.1 Transcription Factor in the Human Forebrain(A–C) Drawing of a coronal section of a 20 GW forebrain with distribution pattern of immunolabeled Nkx2.1+ cells. (B) MGE and cortical VZ/SVZ. (C) In situ (FISH) signal for mRNA Nkx2.1 (red) in the whole cerebral cortex at midterm.(D) In situ hybridization (red) and immunolabeling with Nkx2.1 antibody (green) show colocalization of mRNA and protein.(E and F) (E) mRNA Nkx2.1 (red) and Gad67 immunolabeling (green) in the same cells; (F) mRNA Gad67 (red) and Nkx2.1 immunolabeling (green) in the same cells. (G) Graphs demonstrating the percentage of Nkx2.1+ cells from total number of cells in three gestational ages (15, 18–19, and 22 GW) and two regions: ventricular zone (VZ) and subventricular zone (SVZ).(H) RT-PCR of human cortical tissue for Nkx2.1 and Lhx6 in three stages: 16, 18, and 19 GW; y axis, values represent fold increase normalized to 16 GW values.(I) Western blot for transcription factors at 18 GW in the cortex (Cx) and ganglionic eminence (GE).CP, cortical plate; VZ, ventricular zone; SVZ, subventricular zone. Scale bars represent 200 μm (B) and 50 μm (C–F) 50μm; insets in (D–F) represent 10 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4306459&req=5

Figure 1: The Expression of Nkx2.1 Transcription Factor in the Human Forebrain(A–C) Drawing of a coronal section of a 20 GW forebrain with distribution pattern of immunolabeled Nkx2.1+ cells. (B) MGE and cortical VZ/SVZ. (C) In situ (FISH) signal for mRNA Nkx2.1 (red) in the whole cerebral cortex at midterm.(D) In situ hybridization (red) and immunolabeling with Nkx2.1 antibody (green) show colocalization of mRNA and protein.(E and F) (E) mRNA Nkx2.1 (red) and Gad67 immunolabeling (green) in the same cells; (F) mRNA Gad67 (red) and Nkx2.1 immunolabeling (green) in the same cells. (G) Graphs demonstrating the percentage of Nkx2.1+ cells from total number of cells in three gestational ages (15, 18–19, and 22 GW) and two regions: ventricular zone (VZ) and subventricular zone (SVZ).(H) RT-PCR of human cortical tissue for Nkx2.1 and Lhx6 in three stages: 16, 18, and 19 GW; y axis, values represent fold increase normalized to 16 GW values.(I) Western blot for transcription factors at 18 GW in the cortex (Cx) and ganglionic eminence (GE).CP, cortical plate; VZ, ventricular zone; SVZ, subventricular zone. Scale bars represent 200 μm (B) and 50 μm (C–F) 50μm; insets in (D–F) represent 10 μm.
Mentions: To analyze Nkx2.1 gene expression in the cerebral cortex, we studied human and macaque monkey fetal forebrain tissue at the comparable midgestational stages. We found out that Nkx2.1 was expressed in a decreasing gradient, from high in the medial ganglionic eminence (MGE) to low in the cortical wall, on coronal sections cut through the middle of the telencephalon (Figures 1A–1C). We quantified immunolabeled Nkx2.1+ cells (15–22 gestational weeks [GW]; n = 6). In particular, a higher percentage of Nkx2.1+ cells was observed in the cortical SVZ compared to the VZ (Figure 1G). At 15 GW, 4.2% and 9% of cells were Nkx2.1+ in the VZ and SVZ, respectively; at 18–19 GW, 4.9% and 7.8%; and at 22 GW, 2.6% and 6.4% (Figure 1G). These values probably underestimate the real number of cortical Nkx2.1+ cells, since we applied restrictive counting criteria including only cells with the brightest signal.

Bottom Line: For example, GABAergic interneurons of the mammalian neocortex are generated in the ventral telencephalon and migrate tangentially to the neocortex, in contrast to the projection neurons originating in the ventricular/subventricular zone (VZ/SVZ) of the dorsal telencephalon.The origin, magnitude, and significance of this species-specific difference are not known.Our findings suggest that these progenitors constitute an evolutionary novelty contributing to the elaboration of higher cognitive functions in primates.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA; Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Pasterova 2, 11000 Belgrade, Serbia.

Show MeSH
Related in: MedlinePlus