ArticlePLoS genetics2017
Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- FGF-induced phospholipase Cγ signaling regulates lacrimal gland branching by competing with PI3K in phosphoinositide metabolism.Cell reports · 2025Article
- Crk mediates Csk-Hippo signaling independently of Yap tyrosine phosphorylation to induce cell extrusion.bioRxiv : the preprint server for biology · 2024Article
- Targeting the fibroblast growth factor pathway in molecular subtypes of castration-resistant prostate cancer.The Prostate · 2024Article
- Transcription of microRNAs is regulated by developmental signaling pathways and transcription factors.Frontiers in cell and developmental biology · 2024Article
- Article
- Hypolacrimia and Alacrimia as Diagnostic Features for Genetic or Congenital Conditions.Investigative ophthalmology & visual science · 2022Review
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- Jack of all trades, master of each: the diversity of fibroblast growth factor signalling in eye development.Open biology · 2022Review
- Development of lacrimal gland organoids from iPSC derived multizonal ocular cells.Frontiers in cell and developmental biology · 2022Article
- Lacrimal gland budding requires PI3K-dependent suppression of EGF signaling.Science advances · 2021Article
- Toxicity Evaluation of Long-Term Topical Application of Recombinant Human Keratinocyte Growth Factor-2 Eye Drops onFrontiers in pharmacology · 2021Article
- FGF signaling regulates development by processes beyond canonical pathways.Genes & development · 2020Article
- Etv transcription factors functionally diverge from their upstream FGF signaling in lens development.eLife · 2020Article
- Transcription Factors of the Alx Family: Evolutionarily Conserved Regulators of Deuterostome Skeletogenesis.Frontiers in genetics · 2020Review
- Lens differentiation is controlled by the balance between PDGF and FGF signaling.PLoS biology · 2019Article
- MAPK and PI3K signaling: At the crossroads of neural crest development.Developmental biology · 2018Review
- FGF-induced Pea3 transcription factors program the genetic landscape for cell fate determination.PLoS genetics · 2018Article
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Authors and funding
9 authors at 7 institutions in 3 countries.
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Abstract
The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element conserved in terrestrial but not aquatic animals, underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development.
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