ArticlePLoS genetics2016
Competition between Jagged-Notch and Endothelin1 Signaling Selectively Restricts Cartilage Formation in the Zebrafish Upper Face.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed, 74 citations in OpenAlex.
- Notch receptors involved in the choice between intestinal secretory and enterocytes and differentiation of Bestrophin4 cells.Developmental biology · 2026Article
- Facial Cartilage Development in Jawed Fish.Development & reproduction · 2026Review
- The alx gene family confers segmental identity to frontonasal cranial neural crest cells.Nature communications · 2026Article
- Crip2 preserves hematopoietic stem and progenitor cell production through inhibition of Notch signals.Development (Cambridge, England) · 2026Article
- Notch receptors involved in the choice between intestinal secretory and enterocytes and differentiation of Bestrophin 4 cells.bioRxiv : the preprint server for biology · 2025Article
- The ratio of Wnt signaling activity to Sox2 transcription factor levels predicts neuromesodermal fate potential.Development (Cambridge, England) · 2025Article
- Nkx2.7 is a conserved regulator of craniofacial development.Nature communications · 2025Article
- The Gq/11 family of Gα subunits is necessary and sufficient for lower jaw development.Development (Cambridge, England) · 2025Article
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- The subfunctionalization ofFrontiers in cell and developmental biology · 2025Article
- A potential role of Fgf3 for epibranchial formation in zebrafish.Frontiers in cell and developmental biology · 2025Article
- Pax1a-EphrinB2a pathway in the first pharyngeal pouch controls hyomandibular plate formation by promoting chondrocyte formation in zebrafish.Frontiers in cell and developmental biology · 2025Article
- Transforming growth factor beta signaling and craniofacial development: modeling human diseases in zebrafish.Frontiers in cell and developmental biology · 2024Review
- Endothelin signaling in development.Development (Cambridge, England) · 2023Review
- Craniofacial developmental biology in the single-cell era.Development (Cambridge, England) · 2023Review
- Review
- Predicting Modifiers of Genotype-Phenotype Correlations in Craniofacial Development.International journal of molecular sciences · 2023Article
- Control of cranial ectomesenchyme fate by Nr2f nuclear receptors.Development (Cambridge, England) · 2022Article
- Phylogenomics of trophically diverse cichlids disentangles processes driving adaptive radiation and repeated trophic transitions.Ecology and evolution · 2022Article
- Patterning of cartilaginous condensations in the developing facial skeleton.Developmental biology · 2022Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The intricate shaping of the facial skeleton is essential for function of the vertebrate jaw and middle ear. While much has been learned about the signaling pathways and transcription factors that control facial patterning, the downstream cellular mechanisms dictating skeletal shapes have remained unclear. Here we present genetic evidence in zebrafish that three major signaling pathways - Jagged-Notch, Endothelin1 (Edn1), and Bmp - regulate the pattern of facial cartilage and bone formation by controlling the timing of cartilage differentiation along the dorsoventral axis of the pharyngeal arches. A genomic analysis of purified facial skeletal precursors in mutant and overexpression embryos revealed a core set of differentiation genes that were commonly repressed by Jagged-Notch and induced by Edn1. Further analysis of the pre-cartilage condensation gene barx1, as well as in vivo imaging of cartilage differentiation, revealed that cartilage forms first in regions of high Edn1 and low Jagged-Notch activity. Consistent with a role of Jagged-Notch signaling in restricting cartilage differentiation, loss of Notch pathway components resulted in expanded barx1 expression in the dorsal arches, with mutation of barx1 rescuing some aspects of dorsal skeletal patterning in jag1b mutants. We also identified prrx1a and prrx1b as negative Edn1 and positive Bmp targets that function in parallel to Jagged-Notch signaling to restrict the formation of dorsal barx1+ pre-cartilage condensations. Simultaneous loss of jag1b and prrx1a/b better rescued lower facial defects of edn1 mutants than loss of either pathway alone, showing that combined overactivation of Jagged-Notch and Bmp/Prrx1 pathways contribute to the absence of cartilage differentiation in the edn1 mutant lower face. These findings support a model in which Notch-mediated restriction of cartilage differentiation, particularly in the second pharyngeal arch, helps to establish a distinct skeletal pattern in the upper face.
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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.