Abstract:
:The neurodevelopmental origin of hyperactivity disorder has been suggested to involve the dopaminergic system, but the underlying mechanisms are still unknown. Here, transcription factors Lmx1a and Lmx1b are shown to be essential for midbrain dopaminergic (mDA) neuron excitatory synaptic inputs and dendritic development. Strikingly, conditional knockout (cKO) of Lmx1a/b in postmitotic mDA neurons results in marked hyperactivity. In seeking Lmx1a/b target genes, we identify positively regulated Slitrk2 and negatively regulated Slitrk5. These two synaptic adhesion proteins promote excitatory and inhibitory synapses on mDA neurons, respectively. Knocking down Slitrk2 reproduces some of the Lmx1a/b cKO cellular and behavioral phenotypes, whereas Slitrk5 knockdown has opposite effects. The hyperactivity caused by this imbalance in excitatory/inhibitory synaptic inputs on dopamine neurons is reproduced by chronically inhibiting the ventral tegmental area during development using pharmacogenetics. Our study shows that alterations in developing dopaminergic circuits strongly impact locomotor activity, shedding light on mechanisms causing hyperactivity behaviors.
journal_name
Cell Repjournal_title
Cell reportsauthors
Salesse C,Charest J,Doucet-Beaupré H,Castonguay AM,Labrecque S,De Koninck P,Lévesque Mdoi
10.1016/j.celrep.2020.01.084subject
Has Abstractpub_date
2020-02-18 00:00:00pages
2374-2386.e5issue
7issn
2211-1247pii
S2211-1247(20)30118-2journal_volume
30pub_type
杂志文章相关文献
Cell Reports文献大全abstract::Obesity modifies T cell populations in adipose tissue, thereby contributing to adipose tissue inflammation and insulin resistance. Here, we show that Rab4b, a small GTPase governing endocytic trafficking, is pivotal in T cells for the development of these pathological events. Rab4b expression is decreased in adipose T...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.11.083
更新日期:2018-12-18 00:00:00
abstract::Alternatively activated (M2) macrophages promote wound healing but weaken antimicrobial defenses. The mechanisms that enforce macrophage divergence and dictate the phenotypic and metabolic characteristics of M2 macrophages remain elusive. We show that alternative activation with interleukin (IL)-4 induces expression o...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.05.093
更新日期:2019-06-25 00:00:00
abstract::Tumor suppressor p53 regulates transcription of stress-response genes. Many p53 targets remain undiscovered because of uncertainty as to where p53 binds in the genome and the fact that few genes reside near p53-bound recognition elements (REs). Using chromatin immunoprecipitation followed by exonuclease treatment (ChI...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.06.030
更新日期:2014-07-24 00:00:00
abstract::To ensure a successful infection, herpesviruses have developed elegant strategies to counterbalance the host anti-viral responses. Sterile alpha motif and HD domain 1 (SAMHD1) was recently identified as an intrinsic restriction factor for a variety of viruses. Aside from HIV-2 and the related simian immunodeficiency v...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.04.020
更新日期:2019-07-09 00:00:00
abstract::Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC) has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systemat...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.01.040
更新日期:2015-02-24 00:00:00
abstract::Mucosal antigens induce generation of lamina propria plasma cells (PCs) that secrete dimeric immunoglobulin A (IgA) destined for transport across the epithelium. In addition, blood contains monomeric IgA. To study the relationship between mucosal and systemic antibody responses, we took advantage of celiac disease pat...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.08.036
更新日期:2017-09-05 00:00:00
abstract::The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses to environmental cues and metabolic stress. Although altered UPR(er) gene expression appears in rodent and human type 2 diabetic (T2D) islets, the underlyin...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.03.079
更新日期:2016-05-03 00:00:00
abstract::Astroglia regulate neurovascular coupling while engaging in signal exchange with neurons. The underlying cellular machinery is thought to rely on astrocytic Ca2+ signals, but what controls their amplitude and waveform is poorly understood. Here, we employ time-resolved two-photon excitation fluorescence imaging in acu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.02.043
更新日期:2020-03-10 00:00:00
abstract::Impulses generated by a multicellular, bioelectric signaling center termed the sinoatrial node (SAN) stimulate the rhythmic contraction of the heart. The SAN consists of a network of electrochemically oscillating pacemaker cells encased in a heterogeneous connective tissue microenvironment. Although the cellular compo...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.04.075
更新日期:2018-05-22 00:00:00
abstract::There is an urgent need to identify new treatments for fungal infections. By combining sub-lethal concentrations of the known antifungals fluconazole, caspofungin, amphotericin B, terbinafine, benomyl, and cyprodinil with ∼3,600 compounds in diverse fungal species, we generated a deep reservoir of chemical-chemical in...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.10.018
更新日期:2015-11-17 00:00:00
abstract::Sustained canonical Wnt signaling requires the inhibition of glycogen synthase kinase 3 (GSK3) activity by sequestration of GSK3 inside multivesicular endosomes (MVEs). Here, we show that Wnt signaling is increased by the lysosomal inhibitor chloroquine, which causes accumulation of MVEs. A similar MVE expansion and i...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.09.026
更新日期:2012-11-29 00:00:00
abstract::Intratumoral (IT) STING activation results in tumor regression in preclinical models, yet factors dictating the balance between innate and adaptive anti-tumor immunity are unclear. Here, clinical candidate STING agonist ADU-S100 (S100) is used in an IT dosing regimen optimized for adaptive immunity to uncover requirem...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.11.047
更新日期:2018-12-11 00:00:00
abstract::Recent reports suggest that botulinum neurotoxin (BoNT) A, which is widely used clinically to inhibit neurotransmission, can spread within networks of neurons to have distal effects, but this remains controversial. Moreover, it is not known whether other members of this toxin family are transferred between neurons. He...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.06.104
更新日期:2016-08-16 00:00:00
abstract::Despite the comprehensive knowledge on odor coding, our understanding of the relationship between sensory input and behavioral output in Drosophila remains weak. Here, we measure the behavioral responses generated by larval and adult flies in response to 34 fruit odors and find that larval preference for fruit odors d...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.04.085
更新日期:2018-05-22 00:00:00
abstract::Neutrophil polarity relies on local, mutual inhibition to segregate incompatible signaling circuits to the leading and trailing edges. Mutual inhibition alone should lead to cells having strong fronts and weak backs or vice versa. However, analysis of cell-to-cell variation in human neutrophils revealed that back pola...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.04.009
更新日期:2013-05-30 00:00:00
abstract::Whole-body regeneration relies on the re-establishment of body axes for patterning of new tissue. Wnt signaling is required to correctly regenerate tissues along the primary axis in many animals. However, the causal mechanisms that first launch Wnt signaling during regeneration are poorly characterized. We use the aco...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108098
更新日期:2020-09-01 00:00:00
abstract::G-protein-coupled receptors (GPCRs) constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of R...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.10.011
更新日期:2017-10-24 00:00:00
abstract::Understanding how antibiotics impact bacterial metabolism may provide insight into their mechanisms of action and could lead to enhanced therapeutic methodologies. Here, we profiled the metabolome of Escherichia coli after treatment with three different classes of bactericidal antibiotics (?-lactams, aminoglycosides, ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.09.059
更新日期:2015-11-03 00:00:00
abstract::Here, we examine the mechanism by which plasmacytoid dendritic cells (pDCs) and type I interferons promote humoral autoimmunity. In an amyloid-induced experimental autoimmune model, neutrophil depletion enhanced anti-nuclear antibody development, which correlated with heightened IFN-γ production by natural killer (NK)...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.07.021
更新日期:2015-08-18 00:00:00
abstract::During termination of translation, the nascent peptide is first released from the ribosome, which must be subsequently disassembled into subunits in a process known as ribosome recycling. In bacteria, termination and recycling are mediated by the translation factors RF, RRF, EF-G, and IF3, but their precise roles have...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.06.028
更新日期:2017-07-05 00:00:00
abstract::Nuclear factor κB (NF-κB) RelA is the potent transcriptional activator of inflammatory response genes. We stringently defined a list of direct RelA target genes by integrating physical (chromatin immunoprecipitation sequencing [ChIP-seq]) and functional (RNA sequencing [RNA-seq] in knockouts) datasets. We then dissect...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.01.108
更新日期:2020-02-25 00:00:00
abstract::The large number of mutations identified across all cancers represents an untapped reservoir of targets that can be useful for therapeutic targeting if highly selective, mutation-specific reagents are available. We report here our attempt to generate such reagents: monoclonal antibodies against the most common R175H, ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.11.112
更新日期:2018-01-02 00:00:00
abstract::Transcription factor XBP1s, activated by endoplasmic reticulum (ER) stress in a dose-dependent manner, plays a central role in adaptive unfolded protein response (UPR) via direct activation of multiple genes controlling protein refolding. Here, we report that elevation of ER stress above a critical threshold causes ac...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.09.013
更新日期:2018-10-02 00:00:00
abstract::Premature closure of the sutures that connect the cranial bones during development of the mammalian skull results in a phenotype called craniosynostosis. Recently, several craniosynostosis patients with missense mutations within the gene encoding the interleukin-11 receptor (IL-11R) have been described, but the underl...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.09.005
更新日期:2018-10-02 00:00:00
abstract::Primary afferents transduce environmental stimuli into electrical activity that is transmitted centrally to be decoded into corresponding sensations. However, it remains unknown how afferent populations encode different somatosensory inputs. To address this, we performed two-photon Ca2+ imaging from thousands of dorsa...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.04.065
更新日期:2018-05-15 00:00:00
abstract::Fear extinction is a component of cognitive flexibility that is relevant for important psychiatric diseases, but its molecular mechanism is still largely elusive. We established mice lacking the kinesin-4 motor KIF21B as a model for fear extinction defects. Postsynaptic NMDAR-dependent long-term depression (LTD) is sp...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.05.089
更新日期:2018-06-26 00:00:00
abstract::Most tumor cells exhibit obligatory demands for essential amino acids (EAAs), but the regulatory mechanisms whereby tumor cells take up EAAs and EAAs promote malignant transformation remain to be determined. Here, we show that oncogenic MYC, solute carrier family (SLC) 7 member 5 (SLC7A5), and SLC43A1 constitute a fee...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.12.002
更新日期:2017-12-26 00:00:00
abstract::Ethanol is the most common drug of abuse. It exerts its behavioral effects by acting on widespread neural circuits; however, its impact on glial cells is less understood. We show that Drosophila perineurial glia are critical for ethanol tolerance, a simple form of behavioral plasticity. The perineurial glia form the c...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.01.049
更新日期:2018-02-13 00:00:00
abstract::Synaptic efficacy plays crucial roles in neuronal circuit operation and synaptic plasticity. Presynaptic determinants of synaptic efficacy are neurotransmitter content in synaptic vesicles and the number of vesicles undergoing exocytosis at a time. Bursts of presynaptic firings depress synaptic efficacy, mainly due to...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.02.080
更新日期:2018-03-20 00:00:00
abstract::Appropriate regulation of genes that coordinate pancreas progenitor proliferation and differentiation is required for pancreas development. Here, we explore the role of H3K4 methylation and the Trithorax group (TrxG) complexes in mediating gene expression during pancreas development. Disruption of TrxG complex assembl...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.07.035
更新日期:2019-08-13 00:00:00