ArticleNeuron2014
Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous microRNA dysregulation.
Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 95 citations in OpenAlex.
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- Monoallelic de novo variants in DDX17 cause a neurodevelopmental disorder.Brain : a journal of neurology · 2025Article
- Doublecortin restricts neuronal branching by regulating tubulin polyglutamylation.Nature communications · 2025Article
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- "Disruption of Golgi markers by two RILP-directed shRNAs in neurons: a new role for RILP or a neuron-specific off-target phenotype?"bioRxiv : the preprint server for biology · 2023Article
- Endogenous spacing enables co-processing of microRNAs and efficient combinatorial RNAi.Cell reports methods · 2022Article
- CRISPR-Cas13-Mediated Knockdown of Regulator of G-Protein Signaling 8 (RGS8) Does Not Affect Purkinje Cell Dendritic Development.Frontiers in cell and developmental biology · 2022Article
- RISC-y Business: Limitations of Short Hairpin RNA-Mediated Gene Silencing in the Brain and a Discussion of CRISPR/Cas-Based Alternatives.Frontiers in molecular neuroscience · 2022Review
- Epilepsy protein Efhc1/myoclonin1 is expressed in cells with motile cilia but not in neurons or mitotic apparatuses in brain.Scientific reports · 2020Article
- Long non-coding RNA LncKdm2b regulates cortical neuronal differentiation by cis-activating Kdm2b.Protein & cell · 2020Article
- In vivo epigenetic editing of Sema6a promoter reverses transcallosal dysconnectivity caused by C11orf46/Arl14ep risk gene.Nature communications · 2019Article
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- The neuronal migration hypothesis of dyslexia: A critical evaluation 30 years on.The European journal of neuroscience · 2018Review
- Correct Laminar Positioning in the Neocortex Influences Proper Dendritic and Synaptic Development.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Evaluation and control of miRNA-like off-target repression for RNA interference.Cellular and molecular life sciences : CMLS · 2018Review
- Knockout Mice for Dyslexia Susceptibility Gene Homologs KIAA0319 and KIAA0319L have Unaffected Neuronal Migration but Display Abnormal Auditory Processing.Cerebral cortex (New York, N.Y. : 1991) · 2017Article
- The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis.Scientific reports · 2017Article
- Morphological and Molecular Basis of Cytoplasmic Dilation and Swelling in Cortical Migrating Neurons.Brain sciences · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Acute gene inactivation using short hairpin RNA (shRNA, knockdown) in developing brain is a powerful technique to study genetic function; however, discrepancies between knockdown and knockout murine phenotypes have left unanswered questions. For example, doublecortin (Dcx) knockdown but not knockout shows a neocortical neuronal migration phenotype. Here we report that in utero electroporation of shRNA, but not siRNA or miRNA, to Dcx demonstrates a migration phenotype in Dcx knockouts akin to the effect in wild-type mice, suggesting shRNA-mediated off-target toxicity. This effect was not limited to Dcx, as it was observed in Dclk1 knockouts, as well as with a fraction of scrambled shRNAs, suggesting a sequence-dependent but not sequence-specific effect. Profiling RNAs from electroporated cells showed a defect in endogenous let7 miRNA levels, and disruption of let7 or Dicer recapitulated the migration defect. The results suggest that shRNA-mediated knockdown can produce untoward migration effects by altering endogenous miRNA pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.