Nephronectin regulates atrioventricular canal differentiation via Bmp4-Has2 signaling in zebrafish
| Autor: | Felix B. Engel, Benno Jungblut, Tatyana Novoyatleva, Christian Mühlfeld, Machteld J. van Amerongen, Chinmoy Patra, Florian Diehl, Fulvia Ferrazzi, Liliana Schaefer |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Atrioventricular canal Bmp4 Bone Morphogenetic Protein 4 Nephronectin Animals Genetically Modified ddc:570 Internal medicine medicine Animals Glucuronosyltransferase Molecular Biology Zebrafish Research Articles ALCAM DNA Primers Extracellular Matrix Proteins Cardiac Jelly Base Sequence biology Heart development Models Cardiovascular Gene Expression Regulation Developmental Heart Zebrafish Proteins biology.organism_classification Heart Valves Rats Fibulin Cell biology Endocrinology Gene Knockdown Techniques Ectopic expression Endocardial Cushions Signal transduction Hyaluronan Synthases Signal Transduction Developmental Biology |
| Zdroj: | Development (Cambridge, England) |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.067454 |
| Popis: | The extracellular matrix is crucial for organogenesis. It is a complex and dynamic component that regulates cell behavior by modulating the activity, bioavailability and presentation of growth factors to cell surface receptors. Here, we determined the role of the extracellular matrix protein Nephronectin (Npnt) in heart development using the zebrafish model system. The vertebrate heart is formed as a linear tube in which myocardium and endocardium are separated by a layer of extracellular matrix termed the cardiac jelly. During heart development, the cardiac jelly swells at the atrioventricular (AV) canal, which precedes valve formation. Here, we show that Npnt expression correlates with this process. Morpholino-mediated knockdown of Npnt prevents proper valve leaflet formation and trabeculation and results in greater than 85% lethality at 7 days post-fertilization. The earliest observed phenotype is an extended tube-like structure at the AV boundary. In addition, the expression of myocardial genes involved in cardiac valve formation (cspg2, fibulin 1, tbx2b, bmp4) is expanded and endocardial cells along the extended tube-like structure exhibit characteristics of AV cells (has2, notch1b and Alcam expression, cuboidal cell shape). Inhibition of has2 in npnt morphants rescues the endocardial, but not the myocardial, expansion. By contrast, reduction of BMP signaling in npnt morphants reduces the ectopic expression of myocardial and endocardial AV markers. Taken together, our results identify Npnt as a novel upstream regulator of Bmp4-Has2 signaling that plays a crucial role in AV canal differentiation. |
| Databáze: | OpenAIRE |
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