A robust and high-throughput Cre reporting and characterization system for the whole mouse brain

Madisen, Linda; Zwingman, Theresa; Sunkin, Susan M.; Oh, Seung Wook; Zariwala, Hatim A.; Gu, Hongcang; Ng, Lydia; Palmiter, Richard D.; Hawrylycz, Michael; Jones, Allan R.; Lein, Ed; Zeng, Hongkui

doi:10.1038/nn.2467

Cited by 6,104 publications

(5,860 citation statements)

References 45 publications

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“…All experiments were performed according to institutional guidelines approved by the ethics committee of the Hospital Universitario Virgen del Rocio and the European Community (Council Directive 86/609/EEC). Pv Cre (Hippenmeyer et al, 2005), Chat Cre (Rossi et al, 2011), Smo Flox (Long, Zhang, Karp, Yang, & McMahon, 2001), Shh Flox (Lewis et al, 2001), Rosa26R‐Tomato (Madisen et al, 2010), and Rosa26R‐YFP mice (Srinivas et al, 2001) were obtained from Jackson Laboratory (Stocks numbers 8,069, 6,410, 4,526, 4,293, 7,909, and 6,148) and were maintained on their genetic background (B6;129P2, C57BL/6, 129X1/SvJ, and C57BL/6J). Breeding previous lines, we generated Pv Cre/+ ; Smo loxP/loxP (PV‐Smo), Chat Cre/+ ; Smo loxP/loxP (ChAT‐Smo), Pv Cre/+ ; Shh loxP/loxP (PV‐Shh), and Chat Cre/+ ; Shh loxP/loxP (ChAT‐Shh).…”

Section: Methodsmentioning

confidence: 99%

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Sanchez-Garcia

Nieto-González

García-Junco-Clemente

et al. 2018

Aging Cell

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The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast‐spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF‐independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value.

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Section: Methodsmentioning

confidence: 99%

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Sanchez-Garcia

Nieto-González

García-Junco-Clemente

et al. 2018

Aging Cell

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“…To address the cell-autonomous effects of NL2 on astrocyte development, we sparsely deleted NL2 by introducing Cre via PALE in NL2(+/+) or NL2(f/+) or NL2(f/f) mice (NL2 PALE “WT” “HET” or “KO”, respectively). These mice also carried a single allele of the RTM (Ai14) transgene 26 to label Cre positive (Cre+) cells with td-Tomato expression. NL2 expression in td-Tomato/Cre+ astrocytes was greatly diminished and using these mice and PALE, we confirmed the specificity and effectiveness of our shNL2 construct (Extended Data Fig.…”

Section: Astrocytic Nl2 Controls Synaptogenesismentioning

confidence: 99%

Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis

Stogsdill

Ramirez

Liu

et al. 2017

Nature

399

413

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Astrocytes are highly complex glial cells with numerous fine cellular processes which infiltrate the neuropil to interact with synapses. The mechanisms controlling the establishment of astrocytes’ remarkable morphology and how impairing astrocytic infiltration of the neuropil alters synaptic connectivity are largely unknown. Here we find that cortical astrocyte morphogenesis depends on direct contact with neuronal processes and occurs in tune with the growth and activity of synaptic circuits. Neuroligin (NL) family cell adhesion proteins, NL1, NL2, and NL3, which are expressed by cortical astrocytes, control astrocyte morphogenesis through interactions with neuronal neurexins. Furthermore, in the absence of astrocytic NL2, cortical excitatory synapse formation and function is diminished, whereas inhibitory synaptic function is enhanced. Our findings highlight a novel mechanism of action for NLs and link astrocyte morphogenesis to synaptogenesis. Because NL mutations are implicated in various neurological disorders, these findings also offer an astrocyte-based mechanism of neural pathology.

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“…For these experiments, we used mice in which the #123 promoter drives Cre recombinase in olfactory sensory neurons but not in the resident cells of the olfactory bulb (16)(17)(18). The specificity of this driver was confirmed by crossing mice expressing #123-Cre with a strain harbouring the tdTomato reporter (R26 loxP-STOP-loxPtdTomato ) (19). As shown in Fig.…”

Section: Quantification Of Fragile X Granule Componentsmentioning

confidence: 99%

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

et al. 2017

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Local mRNA translation in growing axons allows for rapid and precise regulation of protein expression in response to extrinsic stimuli. However, the role of local translation in mature CNS axons is unknown. Such a mechanism requires the presence of translational machinery and associated mRNAs in circuit-integrated brain axons. Here we use a combination of genetic, quantitative imaging and super-resolution microscopy approaches to show that mature axons in the mammalian brain contain ribosomes, the translational regulator FMRP and a subset of FMRP mRNA targets. This axonal translational machinery is associated with Fragile X granules (FXGs), which are restricted to axons in a stereotyped subset of brain circuits. FXGs and associated axonal translational machinery are present in hippocampus in humans as old as 57 years. This FXGassociated axonal translational machinery is present in adult rats, even when adult neurogenesis is blocked. In contrast, in mouse this machinery is only observed in juvenile hippocampal axons. This differential developmental expression was specific to the hippocampus, as both mice and rats exhibit FXGs in mature axons in the adult olfactory system. Experiments in Fmr1 null mice show that FMRP regulates axonal protein expression but is not required for axonal transport of ribosomes or its target mRNAs. Axonal translational machinery is thus a feature of adult CNS neurons. Regulation of this machinery by FMRP could support complex behaviours in humans throughout life.

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A robust and high-throughput Cre reporting and characterization system for the whole mouse brain

Cited by 6,104 publications

References 45 publications

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

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