Cellular patterns of transcription factor expression in developing cortical interneurons

Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California at San Francisco, San Francisco, CA 94158-2611, USA.
Cerebral Cortex (Impact Factor: 8.67). 08/2006; 16 Suppl 1(Suppl. 1):i82-8. DOI: 10.1093/cercor/bhk003
Source: PubMed

ABSTRACT Most gamma-aminobutyric acidergic interneurons in the neocortex and hippocampus are derived from subpallial progenitors in the medial ganglionic eminence and migrate tangentially to the pallium, where they differentiate into a diverse set of neuronal subtypes. Toward elucidating the mechanisms underlying the generation of interneuron diversity, we have studied in mice the expression patterns in differentiating and mature neocortical interneurons of 8 transcription factors, including 6 homeobox (Dlx1, Dlx2, Dlx5, Arx, Lhx6, Cux2), 1 basic helix-loop-helix, (NPAS1), and 1 bZIP (MafB). Their patterns of expression change during interneuron differentiation and show distinct distributions within interneuron subpopulations in adult neocortex. This study is a first step to define the combinatorial codes of transcription factors that participate in regulating the specification and function of cortical interneuron subtypes.

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    • "Indeed among MGE-derived cells CoupTFII transcript most frequently occurred in cells defined by SOM mRNA expression (cluster 2 Figure 9) likely representing SOM+ interneurons arising from more dorsal MGE progenitors (Fogarty et al., 2007; Flames et al., 2007; Wonders et al., 2008; Sousa et al., 2009). Npas1 is expressed in migrating interneuron precursors (Cobos et al, 2006) and in mature hippocampal interneurons, partially colocalizing with CR and reelin (Erbiel-Sieler et al, 2004). These observation are consistent with our frequent detection of Npas1 mRNA in CGE-derived interneurons, and the fact that hippocampal Npas1 expression is unaffected in Lhx6 mutants (Zhao et al, 2008). "
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    ABSTRACT: Although vastly outnumbered, inhibitory interneurons critically pace and synchronize excitatory principal cell populations to coordinate cortical information processing. Precision in this control relies upon a remarkable diversity of interneurons primarily determined during embryogenesis by genetic restriction of neuronal potential at the progenitor stage. Like their neocortical counterparts, hippocampal interneurons arise from medial and caudal ganglionic eminence (MGE and CGE) precursors. However, while studies of the early specification of neocortical interneurons are rapidly advancing, similar lineage analyses of hippocampal interneurons have lagged. A "hippocampocentric" investigation is necessary as several hippocampal interneuron subtypes remain poorly represented in the neocortical literature. Thus, we investigated the spatiotemporal origins of hippocampal interneurons using transgenic mice that specifically report MGE- and CGE-derived interneurons either constitutively or inducibly. We found that hippocampal interneurons are produced in two neurogenic waves between E9-E12 and E12-E16 from MGE and CGE, respectively, and invade the hippocampus by E14. In the mature hippocampus, CGE-derived interneurons primarily localize to superficial layers in strata lacunosum moleculare and deep radiatum, while MGE-derived interneurons readily populate all layers with preference for strata pyramidale and oriens. Combined molecular, anatomical, and electrophysiological interrogation of MGE/CGE-derived interneurons revealed that MGE produces parvalbumin-, somatostatin-, and nitric oxide synthase-expressing interneurons including fast-spiking basket, bistratified, axo-axonic, oriens-lacunosum moleculare, neurogliaform, and ivy cells. In contrast, CGE-derived interneurons contain cholecystokinin, calretinin, vasoactive intestinal peptide, and reelin including non-fast-spiking basket, Schaffer collateral-associated, mossy fiber-associated, trilaminar, and additional neurogliaform cells. Our findings provide a basic blueprint of the developmental origins of hippocampal interneuron diversity.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 07/2011; 31(30):10948-70. DOI:10.1523/JNEUROSCI.0323-11.2011 · 6.75 Impact Factor
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    • "Quantification At least 6 sections from 3 brains from each genotype were used for quantitative analysis of tangential migration of Lhx6-expressing interneurons. Lhx6 is expressed in the vast majority of cortical interneurons (Cobos et al. 2006). Sections were imaged using an Axioscope with an Axiocam camera and software (Zeiss); contrast and brightness were adjusted with Adobe Photoshop CS4. "
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    ABSTRACT: Cerebral cortical γ-aminobutyric acid (GABA)ergic interneurons originate from the basal forebrain and migrate into the cortex in 2 phases. First, interneurons cross the boundary between the developing striatum and the cortex to migrate tangentially through the cortical primordium. Second, interneurons migrate radially to their correct neocortical layer position. A previous study demonstrated that mice in which the cortical hem was genetically ablated displayed a massive reduction of Cajal-Retzius (C-R) cells in the neocortical marginal zone (MZ), thereby losing C-R cell-generated reelin in the MZ. Surprisingly, pyramidal cell migration and subsequent layering were almost normal. In contrast, we find that the timing of migration of cortical GABAergic interneurons is abnormal in hem-ablated mice. Migrating interneurons both advance precociously along their tangential path and switch prematurely from tangential to radial migration to invade the cortical plate (CP). We propose that the cortical hem is responsible for establishing cues that control the timing of interneuron migration. In particular, we suggest that loss of a repellant signal from the medial neocortex, which is greatly decreased in size in hem-ablated mice, allows the early advance of interneurons and that reduction of another secreted molecule from C-R cells, the chemokine SDF-1/CXCL12, permits early radial migration into the CP.
    Cerebral Cortex 04/2011; 21(4):748-55. DOI:10.1093/cercor/bhq142 · 8.67 Impact Factor
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    • "Increased interneuron cell death could have also accounted for the reduced percentage of interneurons in Fezf2 –/– layer V (Cobos et al., 2006). To investigate this possibility, we performed staining for FluoroJade-C, which broadly labels dying neurons, in wild-type (n = 3) and Fezf2 –/– (n = 3) cortex at P0, P7, and P14, by which time interneuronal abnormalities are distinctly evident (data not shown). "
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    ABSTRACT: In the mammalian cerebral cortex, the developmental events governing the integration of excitatory projection neurons and inhibitory interneurons into balanced local circuitry are poorly understood. We report that different subtypes of projection neurons uniquely and differentially determine the laminar distribution of cortical interneurons. We find that in Fezf2⁻/⁻ cortex, the exclusive absence of subcerebral projection neurons and their replacement by callosal projection neurons cause distinctly abnormal lamination of interneurons and altered GABAergic inhibition. In addition, experimental generation of either corticofugal neurons or callosal neurons below the cortex is sufficient to recruit cortical interneurons to these ectopic locations. Strikingly, the identity of the projection neurons generated, rather than strictly their birthdate, determines the specific types of interneurons recruited. These data demonstrate that in the neocortex individual populations of projection neurons cell-extrinsically control the laminar fate of interneurons and the assembly of local inhibitory circuitry.
    Neuron 02/2011; 69(4):763-79. DOI:10.1016/j.neuron.2011.01.015 · 15.98 Impact Factor
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