Over-activation of BMP signaling in neural crest cells precipitates heart outflow tract septation
| Autor: | Mariana Valente, Jean-François Darrigrand, Bruno Cadot, Glenda Comai, Maxime Petit, Ryuichi Nishinakamura, Daniel S. Osorio, Vanessa Ribes, Pauline Martinez |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Spatial organisation Cardiac neural crest cells urogenital system Mesenchymal stem cell Phosphatase Neural crest Biology Cell biology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure parasitic diseases embryonic structures medicine Transcriptional regulation Outflow 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/548511 |
| Popis: | SummaryEstablishment of separated pulmonary and systemic circulations in vertebrates relies on the key role of neural crest cells (NCC) for the septation of the embryonic cardiac outflow tract (OFT). Absence of NCCs induces OFT septation defects, analogous to a loss of Bone Morphogenetic Proteins (BMPs) activity, though it remains unclear how BMPs control cardiac NCC differentiation and behaviour. To address this question, we monitored cardiac NCC state upon gain in BMP signaling, caused by the deletion ofDullard, using 3D-imaging and single cell transcriptomics. Specific loss ofDullardin the NCC results in premature OFT septation, pulmonary artery obstruction and embryonic death. This is caused by uncontrolled NCC convergence towards the endocardium and asymmetrical myocardial differentiation, promoted by elevated levels of the guiding cueSema3cand decreased levels in mesenchymal trait markers. Furthermore, we unraveled the molecular basis of the zipper-like OFT septation where graded Sema3c expression follow a gradient of BMP activation in NCC along the OFT length. |
| Databáze: | OpenAIRE |
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