A Resource of Cre Driver Lines for Genetic Targeting of GABAergic Neurons in Cerebral Cortex

Taniguchi, Hiroki; He, Miao; Wu, Priscilla; Kim, Sang Yong; Paik, Raehum; Sugino, Ken; Kvitsani, Duda; Fu, Yu; Lu, Juan; Lin, Ying; Miyoshi, Goichi; Shima, Yasuyuki; Fishell, Gord; Nelson, Sacha B.; Huang, Z. Josh

doi:10.1016/j.neuron.2011.07.026

Cited by 1,780 publications

(1,752 citation statements)

References 73 publications

(98 reference statements)

Supporting

Mentioning

1,688

Contrasting

Unclassified

Order By: Relevance

“…Our newly generated drivers include: 1) Nkx2.1-ires-FlpO (Nkx2.1-Flp) for intersectional fate mapping of medial ganglionic eminence and preoptic area progenitors, 2) vasointestinal peptide-ires-FlpO (VIP-Flp) and somatostatin-ires-FlpO (SST-Flp) for dissecting these two broad cell populations, 3) a highly efficient inducible PV-2A-CreER driver which is far superior to the previous version (Taniguchi et al, 2011). The new reporter lines include: 1) an intersectional reporter expressing nuclear-targeted GFP (HG), 2) a high performance intersection-subtraction reporter (IS), 3) a conversion reporter that converts Cre expression to Flp expression, 4) a RGBow reporter that expresses one of three membranetethered fluorescent proteins in a random manner upon Cre-mediated recombination.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Strategies and Tools for Combinatorial Targeting of GABAergic Neurons in Mouse Cerebral Cortex

He¹,

Tucciarone²,

Lee³

et al. 2016

Neuron

Self Cite

View full text Add to dashboard Cite

SummarySystematic genetic access to GABAergic cell types will facilitate studying the function and development of inhibitory circuitry. However, single gene-driven recombinase lines mark relatively broad and heterogeneous cell populations. Although intersectional approaches improve precision, it remains unclear whether they can capture cell types defined by multiple features. Here we demonstrate that combinatorial genetic and viral approaches target restricted GABAergic subpopulations and cell types characterized by distinct laminar location, morphology, axonal projection, and electrophysiological properties. Intersectional embryonic transcription factor drivers allow finer fate mapping of progenitor pools that give rise to distinct GABAergic populations, including laminar cohorts. Conversion of progenitor fate restriction signals to constitutive recombinase expression enables viral targeting of cell types based on their lineage and birth time. Properly designed intersection, subtraction, conversion, and multi-color reporters enhance the precision and versatility of drivers and viral vectors. These strategies and tools will facilitate studying GABAergic neurons throughout the mouse brain. eTOC BlurbHe et al. present strategies and tools for the combinatorial targeting of GABAergic neurons in the mouse brain. Specific cell type targeting can be achieved by combining 2 to 3 driver-reporter alleles with viral vectors that engage multiple cell-defining features.

show abstract

Section: Resultsmentioning

confidence: 99%

“…The generation of a VIP-ires-Cre driver (Taniguchi et al, 2011) allowed a direct demonstration that certain VIP interneurons preferential inhibit other GABAergic neurons (Lee et al, 2013; Page 4 Neuron. Author manuscript; available in PMC 2017 September 21.…”

Section: Vip-flp-mediated Intersectional Targeting Reveals Multiple Smentioning

confidence: 99%

Strategies and Tools for Combinatorial Targeting of GABAergic Neurons in Mouse Cerebral Cortex

He¹,

Tucciarone²,

Lee³

et al. 2016

Neuron

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, AAV encoding a Cre-dependent fluorescent protein, neurotoxin, or chemogenetic tool was injected into the medullary reticular formation ventral part (MdV) of the Vglut2-Cre mouse to label, ablate, or manipulate the glutamatergic circuit from MdV in order to test the roles of MdV in the forelimb movement control [78]. Hundreds of cell type-specific driver mice lines are available [79][80][81][82][83][84][85][86]. Moreover, driver mice lines of Cre/lox system with the combination of other binary systems [87,88], including the tetracycline-regulated gene expression system [89], enable powerful approaches for manipulation of a wide range of neurons in the nervous system with spatial and temporal specificity.…”

Section: Combining Genetic Identity and Spatial Controlmentioning

confidence: 99%

Selective Manipulation of Neural Circuits

Park

Carmel

2016

Neurotherapeutics

View full text Add to dashboard Cite

Unraveling the complex network of neural circuits that form the nervous system demands tools that can manipulate specific circuits. The recent evolution of genetic tools to target neural circuits allows an unprecedented precision in elucidating their function. Here we describe two general approaches for achieving circuit specificity. The first uses the genetic identity of a cell, such as a transcription factor unique to a circuit, to drive expression of a molecule that can manipulate cell function. The second uses the spatial connectivity of a circuit to achieve specificity: one genetic element is introduced at the origin of a circuit and the other at its termination. When the two genetic elements combine within a neuron, they can alter its function. These two general approaches can be combined to allow manipulation of neurons with a specific genetic identity by introducing a regulatory gene into the origin or termination of the circuit. We consider the advantages and disadvantages of both these general approaches with regard to specificity and efficacy of the manipulations. We also review the genetic techniques that allow gain-and loss-of-function within specific neural circuits. These approaches introduce light-sensitive channels (optogenetic) or drug sensitive channels (chemogenetic) into neurons that form specific circuits. We compare these tools with others developed for circuit-specific manipulation and describe the advantages of each. Finally, we discuss how these tools might be applied for identification of the neural circuits that mediate behavior and for repair of neural connections.

show abstract

“…4 B). The cortical GABAergic interneurons comprise a large variety of subtypes with distinct physiological properties associated with different gene expression profiles (Taniguchi et al, 2011). Sst is one of the few endogenous markers of interneuron subtype that is detectable perinatally by immunofluorescence.…”

Section: Characterization Of the Cell Types Expressing Satb1 In The Pmentioning

confidence: 99%

“…To investigate the potential influence of the H-2Z1 transgene on the differentiation of cortical GABAergic interneurons, we compared the cortical expression of two GABAergic interneuron markers, Lhx6 and Sst, in homozygous transgenics to their wild-type littermates. Lhx6 and Sst are expressed from early stages in MGE-derived GABAergic interneurons (Taniguchi et al, 2011). In situ hybridization was used because reliable immunolabeling for Lhx6 or Sst could not be obtained in the cerebral cortex at E18.5 with available antibodies.…”

Section: Interneuron Distribution In the Cerebral Cortex Of Homozygoumentioning

confidence: 99%

Integration of H-2Z1, a Somatosensory Cortex-Expressed Transgene, Interferes with the Expression of theSatb1andTbc1d5Flanking Genes and Affects the Differentiation of a Subset of Cortical Interneurons

Narboux-Nême

Goïame²,

Matteï³

et al. 2012

J. Neurosci.

View full text Add to dashboard Cite

H-2Z1 is an enhancer trap transgenic mouse line in which the lacZ reporter delineates the somatosensory area of the cerebral cortex where it is expressed in a subset of layer IV neurons. In the search of somatosensory specific genes or regulatory sequences, we mapped the H-2Z1 transgene insertion site to chromosome 17, 100 and 460 kb away from Tbc1d5 and Satb1 flanking genes. We show here that insertion of the H-2Z1 transgene results in three distinct outcomes. First, a genetic background-sensitive expression of lacZ in several brain and body structures. While four genes in a 1 Mb region around the insertion are expressed in the barrel cortex, H-2Z1 expression resembles more that of its two direct neighbors. Moreover, H-2Z1 closely reports most of the body and brain expression sites of the Satb1 chromatin remodeling gene including tooth buds, thymic epithelium, pontine nuclei, fastigial cerebellar nuclei, and cerebral cortex. Second, the H-2Z1 transgene causes insertional mutagenesis of Tbc1d5 and Satb1, leading to a strong decrease in their expressions. Finally, insertion of H-2Z1 affects the differentiation of a subset of cortical GABAergic interneurons, a possible consequence of downregulation of Satb1 expression. Thus, the H-2Z1 "somatosensory" transgene is inserted in the regulatory landscape of two genes highly expressed in the developing somatosensory cortex and reports for a subdomain of their expression profiles. Together, our data suggest that regulation of H-2Z1 expression results from local and remote genetic interactions.

show abstract

A Resource of Cre Driver Lines for Genetic Targeting of GABAergic Neurons in Cerebral Cortex

Cited by 1,780 publications

References 73 publications

Strategies and Tools for Combinatorial Targeting of GABAergic Neurons in Mouse Cerebral Cortex

Strategies and Tools for Combinatorial Targeting of GABAergic Neurons in Mouse Cerebral Cortex

Selective Manipulation of Neural Circuits

Integration of H-2Z1, a Somatosensory Cortex-Expressed Transgene, Interferes with the Expression of theSatb1andTbc1d5Flanking Genes and Affects the Differentiation of a Subset of Cortical Interneurons

Contact Info

Product

Resources

About