ArticleScience signaling2011
Genome-wide analysis of a Wnt1-regulated transcriptional network implicates neurodegenerative pathways.
Article in Science signaling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Genome-wide association study meta-analysis of neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration.Communications biology · 2024Pooled it
- Genetic drivers of progression in Alzheimer's disease are distinct from disease risk.Alzheimer's research & therapy · 2026Article
- Excess Wnt in neurological disease.The Biochemical journal · 2025Review
- Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain.American journal of human genetics · 2024Article
- Modelling TDP-43 proteinopathy in Drosophila uncovers shared and neuron-specific targets across ALS and FTD relevant circuits.Acta neuropathologica communications · 2023Article
- Network-based approaches for modeling disease regulation and progression.Computational and structural biotechnology journal · 2023Review
- Biophysical Survey of Small-Molecule β-Catenin Inhibitors: A Cautionary Tale.Journal of medicinal chemistry · 2022Review
- Loss of IRF2BPL impairs neuronal maintenance through excess Wnt signaling.Science advances · 2022Article
- Wnt/β-Catenin-Dependent Transcription in Autism Spectrum Disorders.Frontiers in molecular neuroscience · 2021Review
- Postnatal Ethanol-Induced Neurodegeneration Involves CB1R-Mediated β-Catenin Degradation in Neonatal Mice.Brain sciences · 2020Article
- Chromatin Decondensation by FOXP2 Promotes Human Neuron Maturation and Expression of Neurodevelopmental Disease Genes.Cell reports · 2019Article
- Wnt/β-catenin signaling stimulates the expression and synaptic clustering of the autism-associated Neuroligin 3 gene.Translational psychiatry · 2018Article
- Species-specific developmental timing is maintained by pluripotent stem cells ex utero.Developmental biology · 2017Article
- Increased Wnt Signaling and Reduced Viability in a Neuronal Model of Progranulin-Deficient Frontotemporal Lobar Degeneration.Molecular neurobiology · 2016Article
- Transcriptomic signatures of neuronal differentiation and their association with risk genes for autism spectrum and related neuropsychiatric disorders.Translational psychiatry · 2016Article
- Early Transcriptional Changes Induced by Wnt/Neural plasticity · 2016Article
- Stem cell guidance through the mechanistic target of rapamycin.World journal of stem cells · 2015Review
- Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders.Nature reviews. Genetics · 2015Review
- Systems biology of neurodegenerative diseases.Integrative biology : quantitative biosciences from nano to macro · 2015Review
- Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease.Neural regeneration research · 2015Review
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
Wnt proteins are critical to mammalian brain development and function. The canonical Wnt signaling pathway involves the stabilization and nuclear translocation of β-catenin; however, Wnt also signals through alternative, noncanonical pathways. To gain a systems-level, genome-wide view of Wnt signaling, we analyzed Wnt1-stimulated changes in gene expression by transcriptional microarray analysis in cultured human neural progenitor (hNP) cells at multiple time points over a 72-hour time course. We observed a widespread oscillatory-like pattern of changes in gene expression, involving components of both the canonical and the noncanonical Wnt signaling pathways. A higher-order, systems-level analysis that combined independent component analysis, waveform analysis, and mutual information-based network construction revealed effects on pathways related to cell death and neurodegenerative disease. Wnt effectors were tightly clustered with presenilin1 (PSEN1) and granulin (GRN), which cause dominantly inherited forms of Alzheimer's disease and frontotemporal dementia (FTD), respectively. We further explored a potential link between Wnt1 and GRN and found that Wnt1 decreased GRN expression by hNPs. Conversely, GRN knockdown increased WNT1 expression, demonstrating that Wnt and GRN reciprocally regulate each other. Finally, we provided in vivo validation of the in vitro findings by analyzing gene expression data from individuals with FTD. These unbiased and genome-wide analyses provide evidence for a connection between Wnt signaling and the transcriptional regulation of neurodegenerative disease genes.
Indexed as
Identifiers
What OpenQuestion holds
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.