ArticleBMC developmental biology2008
The small molecule Mek1/2 inhibitor U0126 disrupts the chordamesoderm to notochord transition in zebrafish.
Article in BMC developmental biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 45 citations in OpenAlex.
- Downstream branches of receptor tyrosine kinase signaling act interdependently to shape the face.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Sclerotome-derived PDGF signaling functions as a niche cue responsible for primitive erythropoiesis.Development (Cambridge, England) · 2023Article
- Zebrafish in dermatology: a comprehensive review of their role in investigating abnormal skin pigmentation mechanisms.Frontiers in physiology · 2023Review
- Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish.Scientific reports · 2021Article
- Chromatin remodeller CHD7 is required for GABAergic neuron development by promoting PAQR3 expression.EMBO reports · 2021Article
- JNK Mediates Differentiation, Cell Polarity and Apoptosis During Amphioxus Development by Regulating Actin Cytoskeleton Dynamics and ERK Signalling.Frontiers in cell and developmental biology · 2021Article
- Article
- SFI Enhances Therapeutic Efficiency of Gefitinib: An Insight into Reversal of Resistance to Targeted Therapy in Non-small Cell Lung Cancer Cells.Journal of Cancer · 2020Article
- Deficiency in the membrane protein Tmbim3a/Grinaa initiates cold-induced ER stress and cell death by activating an intrinsic apoptotic pathway in zebrafish.The Journal of biological chemistry · 2019Article
- An insulin signaling feedback loop regulates pancreas progenitor cell differentiation during islet development and regeneration.Developmental biology · 2016Article
- The cerebral cavernous malformation proteins CCM2L and CCM2 prevent the activation of the MAP kinase MEKK3.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Oncogenic KRAS promotes malignant brain tumors in zebrafish.Molecular cancer · 2015Article
- U0126 protects cells against oxidative stress independent of its function as a MEK inhibitor.ACS chemical neuroscience · 2015Article
- Loss of col8a1a function during zebrafish embryogenesis results in congenital vertebral malformations.Developmental biology · 2014Article
- Impaired embryonic motility in dusp27 mutants reveals a developmental defect in myofibril structure.Disease models & mechanisms · 2014Article
- C2orf62 and TTC17 are involved in actin organization and ciliogenesis in zebrafish and human.PloS one · 2014Article
- Chemical genomics for studying parasite gene function and interaction.Trends in parasitology · 2013Review
- Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21.Nature communications · 2013Article
- Crosstalk between Fgf and Wnt signaling in the zebrafish tailbud.Developmental biology · 2012Article
- Kita driven expression of oncogenic HRAS leads to early onset and highly penetrant melanoma in zebrafish.PloS one · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundKey molecules involved in notochord differentiation and function have been identified through genetic analysis in zebrafish and mice, but MEK1 and 2 have so far not been implicated in this process due to early lethality (Mek1-/-) and functional redundancy (Mek2-/-) in the knockout animals.
resultsHere, we reveal a potential role for Mek1/2 during notochord development by using the small molecule Mek1/2 inhibitor U0126 which blocks phosphorylation of the Mek1/2 target gene Erk1/2 in vivo. Applying the inhibitor from early gastrulation until the 18-somite stage produces a specific and consistent phenotype with lack of dark pigmentation, shorter tail and an abnormal, undulated notochord. Using morphological analysis, in situ hybridization, immunhistochemistry, TUNEL staining and electron microscopy, we demonstrate that in treated embryos the chordamesoderm to notochord transition is disrupted and identify disorganization in the medial layer of the perinotochordal basement mebrane as the probable cause of the undulations and bulges in the notochord. We also examined and excluded FGF as the upstream signal during this process.
conclusionUsing the small chemical U0126, we have established a novel link between MAPK-signaling and notochord differentiation. Our phenotypic analysis suggests a potential connection between the MAPK-pathway, the COPI-mediated intracellular transport and/or the copper-dependent posttranslational regulatory processes during notochord differentiation.
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.