Syndecan contributes to heart cell specification and lumen formation during Drosophila cardiogenesis

Abstract

The transmembrane proteoglycan Syndecan contributes to cell surface signaling of diverse ligands in mammals, yet in Drosophila, genetic evidence links Syndecan only to the Slit receptor Roundabout and to the receptor tyrosine phosphatase LAR. Here we characterize the requirement for syndecan in the determination and morphogenesis of the Drosophila heart, and reveal two phases of activity, indicating that Syndecan is a co-factor in at least two signaling events in this tissue. There is a stochastic failure to determine heart cell progenitors in a subset of abdominal hemisegments in embryos mutant for syndecan, and subsequent to Syndecan depletion by RNA interference. This phenotype is sensitive to gene dosage in the FGF receptor (Heartless), its ligand, Pyramus, as well as BMP-ligand Decapentaplegic (Dpp) and co-factor Sara. Syndecan is also required for lumen formation during assembly of the heart vessel, a phenotype shared with mutations in the Slit and Integrin signaling pathways. Phenotypic interactions of syndecan with slit and Integrin mutants suggest intersecting function, consistent with Syndecan acting as a co-receptor for Slit in the Drosophila heart.

Synchronous and symmetric migration of Drosophila caudal visceral mesoderm cells requires dual input by two FGF ligands

“…We suggest that as cells move towards the anterior, they contribute to establishment of the FGF activity gradient, as has been proposed for other isotropically expressed cell migration guidance cues (Streichan et al, 2011), and could explain how G447-Gal4-mediated expression of ligands within the CVM cells supports rescue. It is thought that FGF ligands interact with the FGFR as a heterotrimeric complex with heparan sulfate proteoglycans (HSPGs) (Knox et al, 2011;Lin et al, 1999). Therefore, another possibility is that an HSPG, or other similar molecule necessary to promote effective FGF-FGFR interactions, is differentially expressed within the TVM and contributes to anteriorly directed movement of CVM cells.…”

Methods to assess Drosophila heart development, function and aging

“…In Drosophila , many fluorescent reporter lines such as Moesin-RFP/Actin-GFP exist and have been successfully applied to study aspects of heart tube assembly (Knox et al 2011, Medioni et al 2008, Vanderploeg et al 2012). The dorsal, subcutaneous location of the heart allows easily obtainable high-quality confocal images of the heart as it undergoes morphogenesis.…”

Drosophila Model of Congenital Heart Diseases

“…For example, co-receptors might play an important role in defining pathway sensitivity and downstream activity. In Drosophila, cardiac Slit/Robo signaling has been shown to require the activity of the heparan sulfate proteoglycan Syndecan (Knox et al, 2011). Since Syndecan is involved in angiogenesis (through VEGF, Chen et al, 2004) and is also upregulated during cardiac remodeling after myocardial infarction, the Drosophila model might help identify important components of Syndecan signaling in these disease-relevant contexts.…”