ArticleDevelopment (Cambridge, England)2013
Mastermind-like transcriptional co-activator-mediated Notch signaling is indispensable for maintaining conjunctival epithelial identity.
Article in Development (Cambridge, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Crk mediates Csk-Hippo signaling independently of Yap tyrosine phosphorylation to induce cell extrusion.bioRxiv : the preprint server for biology · 2024Article
- Plasticity of ocular surface epithelia: Using a murine model of limbal stem cell deficiency to delineate metaplasia and transdifferentiation.Stem cell reports · 2022Article
- NGS Analysis Confirms CommonInternational journal of molecular sciences · 2021Article
- The Partial Role of KLF4 and KLF5 in Gastrointestinal Tumors.Gastroenterology research and practice · 2021Review
- EOFAZ inhibits endothelial‑to‑mesenchymal transition through downregulation of KLF4.International journal of molecular medicine · 2020Article
- Dupilumab-Associated Mucin Deficiency (DAMD).Translational vision science & technology · 2020Article
- Conjunctival goblet cells: Ocular surface functions, disorders that affect them, and the potential for their regeneration.The ocular surface · 2020Review
- Article
- FGF-induced Pea3 transcription factors program the genetic landscape for cell fate determination.PLoS genetics · 2018Article
- The Joubert syndrome protein ARL13B binds tubulin to maintain uniform distribution of proteins along the ciliary membrane.Journal of cell science · 2018Article
- Cancer stem cells in hepatocellular carcinoma: an overview and promising therapeutic strategies.Therapeutic advances in medical oncology · 2018Review
- Lacrimal gland development: From signaling interactions to regenerative medicine.Developmental dynamics : an official publication of the American Association of Anatomists · 2017Review
- Goblet cells of the conjunctiva: A review of recent findings.Progress in retinal and eye research · 2016Review
- Primary cilia maintain corneal epithelial homeostasis by regulation of the Notch signaling pathway.Development (Cambridge, England) · 2016Article
- Notch Signaling in Meibomian Gland Epithelial Cell Differentiation.Investigative ophthalmology & visual science · 2016Article
- Activation of Dll4/Notch Signaling and Hypoxia-Inducible Factor-1 Alpha Facilitates Lymphangiogenesis in Lacrimal Glands in Dry Eye.PloS one · 2016Article
- Wakayama symposium: role of canonical Notch signaling in conjucntival goblet cell differentiation and dry eye syndrome.BMC ophthalmology · 2015Article
- The Krüppel-like factors in female reproductive system pathologies.Journal of molecular endocrinology · 2015Review
- Characterization of ex vivo cultured limbal, conjunctival, and oral mucosal cells: A comparative study with implications in transplantation medicine.Molecular vision · 2015Article
- TGFβ signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium.Development (Cambridge, England) · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Conjunctival goblet cells primarily synthesize mucins to lubricate the ocular surface, which is essential for normal vision. Notch signaling has been known to associate with goblet cell differentiation in intestinal and respiratory tracts, but its function in ocular surface has yet to be fully characterized. Herein, we demonstrate that conditional inhibition of canonical Notch signaling by expressing dominant negative mastermind-like 1 (dnMaml1) in ocular surface epithelia resulted in complete suppression of goblet cell differentiation during and subsequent to development. When compared with the ocular surface of wild-type mice (OS(Wt)), expression of dnMaml1 at the ocular surface (OS(dnMaml1)) caused conjunctival epithelial hyperplasia, aberrant desquamation, failure of Mucin 5ac (Muc5ac) synthesis, subconjunctival inflammation and epidermal metaplasia in cornea. In addition, conditional deletion of Notch1 from the ocular surface epithelia partially recapitulated OS(dnMaml1) phenotypes. We have demonstrated that N1-ICD (Notch1 intracellular domain) transactivated the mouse Krüppel-like factor 4 (Klf) promoter and that Klf4 directly bound to and significantly potentiated the Muc5ac promoter. By contrast, OS(dnMaml1) dampened Klf4 and Klf5 expression, and diminished Muc5ac synthesis. Collectively, these findings indicated that Maml-mediated Notch signaling plays a pivotal role in the initiation and maintenance of goblet cell differentiation for normal ocular surface morphogenesis and homeostasis through regulation of Klf4 and Klf5.
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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.