Alcama mediates Edn1 signaling during zebrafish cartilage morphogenesis
Open accessAbstract
The zebrafish pharyngeal cartilage is derived from the pharyngeal apparatus, a vertebrate-specific structure derived from all three germ layers. Developmental aberrations of the pharyngeal apparatus lead to birth defects such as Treacher-Collins and DiGeorge syndromes. While interactions between endoderm and neural crest (NC) are known to be important for cartilage formation, the full complement of molecular players involved and their roles remain to be elucidated. Activated leukocyte cell adhesion molecule a (alcama), a member of the immunoglobulin (Ig) superfamily, is among the prominent markers of pharyngeal pouch endoderm, but to date no role has been assigned to this adhesion molecule in the development of the pharyngeal apparatus. Here we show that alcama plays a crucial, non-autonomous role in pharyngeal endoderm during zebrafish cartilage morphogenesis. alcama knockdown leads to defects in NC differentiation, without affecting NC specification or migration. These defects are reminiscent of the phenotypes observed when Endothelin 1 (Edn1) signaling, a key regulator of cartilage development is disrupted. Using gene expression analysis and rescue experiments we show that Alcama functions downstream of Edn1 signaling to regulate NC differentiation and cartilage morphogenesis. In addition, we also identify a role for neural adhesion molecule 1.1 (nadl1.1), a known interacting partner of Alcama expressed in neural crest, in NC differentiation. Our data shows that nadl1.1 is required for alcama rescue of NC differentiation in edn1(-/-) mutants and that Alcama interacts with Nadl1.1 during chondrogenesis. Collectively our results support a model by which Alcama on the endoderm interacts with Nadl1.1 on NC to mediate Edn1 signaling and NC differentiation during chondrogenesis.
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alcama has been found to mediate endothelin 1 signaling in cartilage development.
“It is intriguing that alcama has been found to mediate endothelin 1 signaling in cartilage development [58].”
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Higdon, C. W., Mitra, R. D., & Johnson, S. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067801 · Cited by 125 · see citing works
- Authors
- Choudhry, P., Joshi, D., Funke, B., & Trede, N.
- Affiliations
- University of Utah (US)
- Harvard University (US)
- Corresponding author
- Trede, Nikolaus
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 349
- Issue
- 2
- Pages
- 483-493
- ISSN
- 0012-1606 (ISSN-L)
- PMC
- PMC3036164
- OpenAlex
- W2004473945
- Cited by
- 13
- References
- 0
- Citations by year
- 2026: 1 · 2024: 1 · 2017: 3 · 2016: 1 · 2013: 5 · 2012: 1
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- R01 HD047863-01
- Huntsman Cancer Foundation (P30 CA042014)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
- Keywords
- endothelin-1 signaling, cartilage morphogenesis, neural crest differentiation, chondrogenesis, pharyngeal endoderm, Treacher Collins syndrome, 22q11.2 deletion syndrome, zebrafish
- MeSH terms
- Animals, Branchial Region, Cell Differentiation, Cloning, Molecular, Immunohistochemistry, Leupeptins, Models, Biological, Neural Crest, Zebrafish, Signal Transduction, In Situ Hybridization, Fluorescence, DNA Primers, Neural Cell Adhesion Molecules, Endothelin-1, Chondrogenesis, Activated-Leukocyte Cell Adhesion Molecule, Gene Expression Profiling, Zebrafish Proteins, Gene Knockout Techniques
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