ArticlePLoS genetics2012
Loss of Tgif function causes holoprosencephaly by disrupting the SHH signaling pathway.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 79 citations in OpenAlex.
- Transcriptional repression by TGIF2 coordinates neurogenic priming and neural stem cell maintenance.Science advances · 2026Article
- Evolutionary divergence in CTCF-mediated chromatin topology drives transcriptional innovation in humans.Nature communications · 2025Article
- Small molecule valproic acid enhances ventral patterning of human neural tube organoids by regulating Wnt and Shh signalling.Cell proliferation · 2025Article
- Identification of conserved skeletal enhancers associated with craniosynostosis risk genes.Human molecular genetics · 2024Article
- Cell fate decisions, transcription factors and signaling during early retinal development.Progress in retinal and eye research · 2022Review
- Article
- Mutations in phospholipase C eta-1 (Journal of medical genetics · 2022Article
- Familial microdeletion 18p11.32 to 18p11.31 in a Chinese family with normal phenotype.Molecular cytogenetics · 2022Article
- Solitary Median Maxillary Central Incisor Syndrome: An Exploration of the Pathogenic Mechanism.Frontiers in genetics · 2022Article
- Structural Insight into the Binding of TGIF1 to SIN3A PAH2 Domain through a C-Terminal Amphipathic Helix.International journal of molecular sciences · 2021Article
- Diabetes, Oxidative Stress, and DNA Damage Modulate Cranial Neural Crest Cell Development and the Phenotype Variability of Craniofacial Disorders.Frontiers in cell and developmental biology · 2021Review
- TGIF1 Knockdown Inhibits the Proliferation and Invasion of Gastric Cancer via AKT Signaling Pathway.Cancer management and research · 2021Article
- Posttranslational Modifications in Conserved Transcription Factors: A Survey of the TALE-Homeodomain Superclass in Human and Mouse.Frontiers in cell and developmental biology · 2021Review
- Reprogramming Axial Level Identity to Rescue Neural-Crest-Related Congenital Heart Defects.Developmental cell · 2020Article
- Developmental exposure to PbChemosphere · 2020Article
- SHH signaling mediated by a prechordal and brain enhancer controls forebrain organization.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- TGIF1 functions as a tumor suppressor in pancreatic ductal adenocarcinoma.The EMBO journal · 2019Article
- TGIF transcription factors repress acetyl CoA metabolic gene expression and promote intestinal tumor growth.Genes & development · 2019Article
- Functions of TGIF homeodomain proteins and their roles in normal brain development and holoprosencephaly.American journal of medical genetics. Part C, Seminars in medical genetics · 2018Article
- Extracephalic manifestations of nonchromosomal, nonsyndromic holoprosencephaly.American journal of medical genetics. Part C, Seminars in medical genetics · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Holoprosencephaly (HPE) is a severe human genetic disease affecting craniofacial development, with an incidence of up to 1/250 human conceptions and 1.3 per 10,000 live births. Mutations in the Sonic Hedgehog (SHH) gene result in HPE in humans and mice, and the Shh pathway is targeted by other mutations that cause HPE. However, at least 12 loci are associated with HPE in humans, suggesting that defects in other pathways contribute to this disease. Although the TGIF1 (TG-interacting factor) gene maps to the HPE4 locus, and heterozygous loss of function TGIF1 mutations are associated with HPE, mouse models have not yet explained how loss of Tgif1 causes HPE. Using a conditional Tgif1 allele, we show that mouse embryos lacking both Tgif1 and the related Tgif2 have HPE-like phenotypes reminiscent of Shh null embryos. Eye and nasal field separation is defective, and forebrain patterning is disrupted in embryos lacking both Tgifs. Early anterior patterning is relatively normal, but expression of Shh is reduced in the forebrain, and Gli3 expression is up-regulated throughout the neural tube. Gli3 acts primarily as an antagonist of Shh function, and the introduction of a heterozygous Gli3 mutation into embryos lacking both Tgif genes partially rescues Shh signaling, nasal field separation, and HPE. Tgif1 and Tgif2 are transcriptional repressors that limit Transforming Growth Factor β/Nodal signaling, and we show that reducing Nodal signaling in embryos lacking both Tgifs reduces the severity of HPE and partially restores the output of Shh signaling. Together, these results support a model in which Tgif function limits Nodal signaling to maintain the appropriate output of the Shh pathway in the forebrain. These data show for the first time that Tgif1 mutation in mouse contributes to HPE pathogenesis and provide evidence that this is due to disruption of the Shh pathway.
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.