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Alcama mediates Edn1 signaling during zebrafish cartilage morphogenesis

Choudhry, Priya and Joshi, Deepa and Funke, Birgit and Trede, Nikolaus (2011) Alcama mediates Edn1 signaling during zebrafish cartilage morphogenesis. Developmental Biology, 349 (2). pp. 483-493. ISSN 0012-1606. PMCID PMC3036164.

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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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Additional Information:Copyright © 2010 Elsevier. Received for publication 9 September 2010. Revised 1 November 2010. Accepted 3 November 2010. Available online 10 November 2010. The authors wish to thank Raju Kucherlapati and Len Zon for material and technical support, Sarah Hutchinson for intellectual contributions, and Gavin Wright (and his student) for technical expertise. We wish to thank Chuck Kimmel for Alcian Blue-stained furina−/− mutant zebrafish, and Gage Crump for dlx plasmids. This work was supported in part by R01 HD047863-01 and by the Huntsman Cancer Foundation. Huntsman Cancer Institute core facilities, supported by grant P30 CA042014, also facilitated this work.
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NIHR01 HD047863-01
Huntsman Cancer FoundationUNSPECIFIED
National Cancer InstituteP30 CA042014
Issue or Number:2
PubMed Central ID:PMC3036164
Record Number:CaltechAUTHORS:20140416-132511544
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ID Code:44983
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Deposited On:21 Apr 2014 23:46
Last Modified:03 Oct 2019 06:25

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