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Cited by 179Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationNeuroscience and Neuropharmacology Research

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A Wide Diversity of Cortical GABAergic Interneurons Derives from the Embryonic Preoptic Area

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Gelman, Diego, Griveau, Amélie, Dehorter, Nathalie, Teissier, Anne, Varela, Carolina, Pla, Ramón, Pierani, Alessandra, Marín, Oscar·2011·The Journal of Neuroscience
DOI 10.1523/jneurosci.4068-11.2011PMC PMC6633309
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Abstract

GABA-containing (GABAergic) interneurons comprise a very heterogeneous group of cells that are crucial for cortical function. Different classes of interneurons specialize in targeting specific subcellular domains of excitatory pyramidal cells or other interneurons, which provides cortical circuits with an enormous capability for information processing. As in other regions of the CNS, cortical interneuron diversity is thought to emerge from the genetic specification of different groups of progenitor cells within the subpallium. Most cortical interneurons originate from two main regions, the medial and the caudal ganglionic eminences (MGE and CGE, respectively). In addition, it has been shown that progenitors in the embryonic preoptic area (POA) also produce a small population of cortical GABAergic interneurons. Here, we show that the contribution of the POA to the complement of cortical GABAergic interneurons is larger than previously believed. Using genetic fate mapping and in utero transplantation experiments, we demonstrate that Dbx1-expressing progenitor cells in the POA give rise to a small but highly diverse cohort of cortical interneurons, with some neurochemical and electrophysiological characteristics that were previously attributed to MGE- or CGE-derived interneurons. There are, however, some features that seem to distinguish POA-derived interneurons from MGE- or CGE-derived cells, such as their preferential laminar location. These results indicate that the mechanisms controlling the specification of different classes of cortical interneurons might be more complex than previously expected. Together with earlier findings, our results also suggest that the POA generates nearly 10% of the GABAergic interneurons in the cerebral cortex of the mouse.

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Figures

Figure 1 YFP expression in the adult telencephalon of Dbx1 Cre ;ROSA26 YFP mice. A , A' , Image of a coronal section through the somatosensory cortex of P30 Dbx1 Cre ;ROSA26 YFP miceinwhichtheoveralllaminar distribution of YFP-expressing cells is visualized. Note that YFP-expressing cells are most abundant in deep layers. The terminal fields of thalamic axons are also labeled with YFP (asterisks). A' , High-magnification image of one of the cells shown in A . Most YFP-expressing cells in the cortex of P30 Dbx1 Cre/ + ; Rosa26R-YFP mice have the morphological features of cortical interneurons. B , Schemas depicting the distribution of YFPexpressing cells containing GABA (red dots) in the neocortex and hippocampus of P30 Dbx1 Cre ;ROSA26 YFP mice at different rostrocaudal levels. C-C' , Immunohistochemistry against YFP ( C , C' ) and GABA ( C' , C' ) in the neocortex of P30 Dbx1 Cre ;ROSA26 YFP mice. Arrowheads indicate YFP/GABA double-labeled cells. D , Quantification of the laminar distribution of YFP/GABA doublelabeled cells in the cortex of Dbx1 Cre ;ROSA26 YFP mice. Layer I: 3.6 ± 0.7%; Layers II/III: 4.3 ± 0.4%; Layer IV: 5.2 ± 1.1%; Layer V: 33.0 ± 1.6%; Layer VI: 53.9 ± 1.8%; n = 3. E , Birth date of GABAergic Dbx1-derived neurons. E10.5: 19.69 ± 4.64%; E11.5: 35.42 ± 1.39%;E12.5: 25.0 ± 1.60%;E14.5: 11.26 ± 4.12%; n = 3. I-VI, Cortical layers I to VI. Scale bars: A , 250 𝛍 m; A' , 25 𝛍 m; C-C' , 100 𝛍 m.
Figure 1 YFP expression in the adult telencephalon of Dbx1 Cre ;ROSA26 YFP mice. A , A' , Image of a coronal section through the somatosensory cortex of P30 Dbx1 Cre ;ROSA26 YFP miceinwhichtheoveralllaminar distribution of YFP-expressing cells is visualized. Note that YFP-expressing cells are most abundant in deep layers. The terminal fields of thalamic axons are also labeled with YFP (asterisks). A' , High-magnification image of one of the cells shown in A . Most YFP-expressing cells in the cortex of P30 Dbx1 Cre/ + ; Rosa26R-YFP mice have the morphological features of cortical interneurons. B , Schemas depicting the distribution of YFPexpressing cells containing GABA (red dots) in the neocortex and hippocampus of P30 Dbx1 Cre ;ROSA26 YFP mice at different rostrocaudal levels. C-C' , Immunohistochemistry against YFP ( C , C' ) and GABA ( C' , C' ) in the neocortex of P30 Dbx1 Cre ;ROSA26 YFP mice. Arrowheads indicate YFP/GABA double-labeled cells. D , Quantification of the laminar distribution of YFP/GABA doublelabeled cells in the cortex of Dbx1 Cre ;ROSA26 YFP mice. Layer I: 3.6 ± 0.7%; Layers II/III: 4.3 ± 0.4%; Layer IV: 5.2 ± 1.1%; Layer V: 33.0 ± 1.6%; Layer VI: 53.9 ± 1.8%; n = 3. E , Birth date of GABAergic Dbx1-derived neurons. E10.5: 19.69 ± 4.64%; E11.5: 35.42 ± 1.39%;E12.5: 25.0 ± 1.60%;E14.5: 11.26 ± 4.12%; n = 3. I-VI, Cortical layers I to VI. Scale bars: A , 250 𝛍 m; A' , 25 𝛍 m; C-C' , 100 𝛍 m.CC-BY-NC-SA · From the PDF
Figure 2 Molecular characterization of progenitor cells in the embryonic POA. A-H , Coronal sections through two different levels of the caudal telencephalon at E11.5 showing the expression of Shh ( A , E ), Dbx1 ( B , F ), Nkx6-2 ( C , G ), and Nkx5-1 ( D , H ) mRNA. In situ images ( A , B ) were pseudo-colored using Photoshop software. A-D and E-H are from the same brain and are adjacent to each other. pSPV, Supraoptic paraventricular progenitor domain. Scale bar, 100 𝛍 m.
Figure 2 Molecular characterization of progenitor cells in the embryonic POA. A-H , Coronal sections through two different levels of the caudal telencephalon at E11.5 showing the expression of Shh ( A , E ), Dbx1 ( B , F ), Nkx6-2 ( C , G ), and Nkx5-1 ( D , H ) mRNA. In situ images ( A , B ) were pseudo-colored using Photoshop software. A-D and E-H are from the same brain and are adjacent to each other. pSPV, Supraoptic paraventricular progenitor domain. Scale bar, 100 𝛍 m.CC-BY-NC-SA · From the PDF
Figure 3 Molecular characterization of Dbx1-derived cells in the embryonic POA. A , B , D , D' , Coronal sections through the telencephalon of E11.5 Dbx1 nlsLacZ/ + embryos showing the expression of Dbx1- ( A ), 𝛃 Gal- ( B , D , D' ), Tbr1- ( A ), Nkx6-2- ( B , D' ), and Nkx2-1- ( D ) expressing cells. The asterisk ( A ) indicates the location of Dbx1-expressing progenitor cells; the arrow in B denotestheextent of the migration of the cells derived from Dbx1-expressing progenitors at this stage. D and D' are high-magnification images of the boxed area in C . Filled arrowheads point to double-labeled cells; open arrowheads point to single-labeled cells. C , Schematic drawing of a hemisection through the telencephalon of an E11.5 mouse embryo showing the distribution of molecularly distinct populations of POA cells. Scale bars, 100 𝛍 m.
Figure 3 Molecular characterization of Dbx1-derived cells in the embryonic POA. A , B , D , D' , Coronal sections through the telencephalon of E11.5 Dbx1 nlsLacZ/ + embryos showing the expression of Dbx1- ( A ), 𝛃 Gal- ( B , D , D' ), Tbr1- ( A ), Nkx6-2- ( B , D' ), and Nkx2-1- ( D ) expressing cells. The asterisk ( A ) indicates the location of Dbx1-expressing progenitor cells; the arrow in B denotestheextent of the migration of the cells derived from Dbx1-expressing progenitors at this stage. D and D' are high-magnification images of the boxed area in C . Filled arrowheads point to double-labeled cells; open arrowheads point to single-labeled cells. C , Schematic drawing of a hemisection through the telencephalon of an E11.5 mouse embryo showing the distribution of molecularly distinct populations of POA cells. Scale bars, 100 𝛍 m.CC-BY-NC-SA · From the PDF
Figure 4 YFP expression in the developing telencephalon of Dbx1 Cre ;ROSA26 YFP embryos. A-E' , Coronal sections through the telencephalon of E13.5 ( A-B' ) and E15.5 ( C-E' ) Dbx1 Cre ;ROSA26 YFP embryos showing the expression of YFP ( A-E ), calbindin (CB; A' , B' , D , E' ), and CR ( C ). B , B' and E , E' , High-magnification images of the boxed areas in A' and D , respectively. CP, cortical plate; SVZ, subventricular zone; VZ, ventricular zone. Filled arrowheads point to double-labeled cells, open arrowheads point to calbindin + /YFP -cells; arrows point to calbindin -/YFP + cells. R26R , ROSA26 YFP . Scale bars: A , A' , C , D (in A ), 100 𝛍 m; B , B' , E , E' (in B' ), 25 𝛍 m.
Figure 4 YFP expression in the developing telencephalon of Dbx1 Cre ;ROSA26 YFP embryos. A-E' , Coronal sections through the telencephalon of E13.5 ( A-B' ) and E15.5 ( C-E' ) Dbx1 Cre ;ROSA26 YFP embryos showing the expression of YFP ( A-E ), calbindin (CB; A' , B' , D , E' ), and CR ( C ). B , B' and E , E' , High-magnification images of the boxed areas in A' and D , respectively. CP, cortical plate; SVZ, subventricular zone; VZ, ventricular zone. Filled arrowheads point to double-labeled cells, open arrowheads point to calbindin + /YFP -cells; arrows point to calbindin -/YFP + cells. R26R , ROSA26 YFP . Scale bars: A , A' , C , D (in A ), 100 𝛍 m; B , B' , E , E' (in B' ), 25 𝛍 m.CC-BY-NC-SA · From the PDF
Figure 5 Dbx1-derived cortical interneurons originate in the POA. A , Schematic diagram of the experimental design. Coronal slices were prepared from the telencephalon of E12.5 Dbx1 Cre ;ROSA26 YFP donor embryos and progenitor cells were isolated from a small cube of tissue from the POA. In parallel, the MGE was dissected from BrdU-injected wild-type embryos and dissociated (these cells served as a control of the transplantation). Pooled donor cells were then injected into the POA of E12.5 host embryos. Host embryos were analyzed at P14. B , Coronal section through the somatosensory cortex of a transplanted P14 mouse showing one Dbx1-derived cell (green) after nuclear staining (DAPI) and immunohistochemistry against YFP. C , C' , High-magnification images of the boxed area in B . Filled arrowheads point to a neuron expressing YFP and GABA; open arrowheads point to a GABA cell that does not derive from the Dbx1 lineage. Scale bars: B , 20 𝛍 m; C , C' (in C ), 50 𝛍 m.
Figure 5 Dbx1-derived cortical interneurons originate in the POA. A , Schematic diagram of the experimental design. Coronal slices were prepared from the telencephalon of E12.5 Dbx1 Cre ;ROSA26 YFP donor embryos and progenitor cells were isolated from a small cube of tissue from the POA. In parallel, the MGE was dissected from BrdU-injected wild-type embryos and dissociated (these cells served as a control of the transplantation). Pooled donor cells were then injected into the POA of E12.5 host embryos. Host embryos were analyzed at P14. B , Coronal section through the somatosensory cortex of a transplanted P14 mouse showing one Dbx1-derived cell (green) after nuclear staining (DAPI) and immunohistochemistry against YFP. C , C' , High-magnification images of the boxed area in B . Filled arrowheads point to a neuron expressing YFP and GABA; open arrowheads point to a GABA cell that does not derive from the Dbx1 lineage. Scale bars: B , 20 𝛍 m; C , C' (in C ), 50 𝛍 m.CC-BY-NC-SA · From the PDF
Figure 6 Neurochemical profile of cortical interneurons derived from Dbx1-expressing progenitor cells. A , B , E , F , H , I , Immunohistochemistry against YFP ( A , B , E , F , H , I ), parvalbumin ( A ), somatostatin ( B ), Reelin ( E ), calretinin ( F ), nitric oxide synthase ( G ), vasoactive intestinal peptide ( H ), neuropeptide Y ( J ), and Lhx6 ( K ) in the neocortex of P30 Dbx1 Cre ;ROSA26 YFP mice. Filled arrowheads point to double-labeled cells; open arrowheads indicate YFP-expressing neurons that do not express the corresponding marker. C , Schemas depicting the distribution of YFP-expressing interneurons containing PV (orange dots) or SST (red dots) in the neocortex and hippocampus of a P30 Dbx1 Cre ;ROSA26 YFP mouse. D , Morphological varieties of FS cortical interneurons in Dbx1 Cre ;ROSA26 YFP mice. The images are Neurolucida reconstructions from recorded neurons-a stuttering FS interneuron in layer V and a continuous FS interneuron in layer VI. I , Quantification of the percentage of colocalization of YFP-expressing cells with different neurochemical markers. Scale bar, 80 𝛍 m.
Figure 6 Neurochemical profile of cortical interneurons derived from Dbx1-expressing progenitor cells. A , B , E , F , H , I , Immunohistochemistry against YFP ( A , B , E , F , H , I ), parvalbumin ( A ), somatostatin ( B ), Reelin ( E ), calretinin ( F ), nitric oxide synthase ( G ), vasoactive intestinal peptide ( H ), neuropeptide Y ( J ), and Lhx6 ( K ) in the neocortex of P30 Dbx1 Cre ;ROSA26 YFP mice. Filled arrowheads point to double-labeled cells; open arrowheads indicate YFP-expressing neurons that do not express the corresponding marker. C , Schemas depicting the distribution of YFP-expressing interneurons containing PV (orange dots) or SST (red dots) in the neocortex and hippocampus of a P30 Dbx1 Cre ;ROSA26 YFP mouse. D , Morphological varieties of FS cortical interneurons in Dbx1 Cre ;ROSA26 YFP mice. The images are Neurolucida reconstructions from recorded neurons-a stuttering FS interneuron in layer V and a continuous FS interneuron in layer VI. I , Quantification of the percentage of colocalization of YFP-expressing cells with different neurochemical markers. Scale bar, 80 𝛍 m.CC-BY-NC-SA · From the PDF
Figure 7 Intrinsic electrophysiological profiles of Dbx1-derived cortical interneurons. A , Voltage responses to short depolarizing current injection (500 ms) at near-threshold (top), threshold (middle), and suprathreshold (bottom) potentials. B , Voltage responses to prolonged step current injection (5 s). Profiles are shown for an sFS interneuron, a cFS interneuron with delayed firing at near-threshold potentials, an IB interneuron that exhibits a burst of two to six spikes, a bAD interneuron that showed a burst of two spikes and a pronounced adaptation, an LS interneuron, and an IS interneuron.
Figure 7 Intrinsic electrophysiological profiles of Dbx1-derived cortical interneurons. A , Voltage responses to short depolarizing current injection (500 ms) at near-threshold (top), threshold (middle), and suprathreshold (bottom) potentials. B , Voltage responses to prolonged step current injection (5 s). Profiles are shown for an sFS interneuron, a cFS interneuron with delayed firing at near-threshold potentials, an IB interneuron that exhibits a burst of two to six spikes, a bAD interneuron that showed a burst of two spikes and a pronounced adaptation, an LS interneuron, and an IS interneuron.CC-BY-NC-SA · From the PDF

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Metadata

Authors
Gelman, D., Griveau, A., Dehorter, N., Teissier, A., Varela, C., Pla, R., Pierani, A., & Marín, O.
Affiliations
  • Consejo Superior de Investigaciones Científicas (ES)
  • Centre National de la Recherche Scientifique (FR)
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2011-11-16
Volume
31
Issue
46
Pages
16570-16580
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.4068-11.2011
PMC
PMC6633309
OpenAlex
W1994924452
Cited by
179
References
51
Citations by year
2026: 3 · 2025: 5 · 2024: 10 · 2023: 14 · 2022: 11 · 2021: 16 · 2020: 23 · 2019: 12 · 2018: 13 · 2017: 18 · 2016: 10 · 2015: 13 · 2014: 8 · 2013: 14 · 2012: 9
FWCI
3.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Americanae (AECID Library) (publishedVersion, other-oa)
  • HAL (submittedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
  • ANU Open Research (Australian National University) (submittedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
Funders
  • Association pour la Recherche sur le Cancer
  • European Commission (005139)
  • Centre National de la Recherche Scientifique
  • Ministerio de Ciencia e Innovación (CSD2007-00023)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
GABAergic interneurons, medial ganglionic eminence, caudal ganglionic eminence, interneuron specification, laminar distribution, mouse cortex, fate mapping, in utero transplantation
MeSH terms
Animals, Animals, Newborn, Bacterial Proteins, Bromodeoxyuridine, Cell Movement, Electric Stimulation, Embryo, Mammalian, gamma-Aminobutyric Acid, Indoles, Interneurons, Luminescent Proteins, Membrane Potentials, Mice, Transgenic, Nerve Tissue Proteins, Preoptic Area, Proteins, Somatosensory Cortex, Homeodomain Proteins, Patch-Clamp Techniques, Gene Expression Regulation, Developmental, RNA, Untranslated, Green Fluorescent Proteins, Mice, Neural Stem Cells, In Vitro Techniques

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