Tbx1 regulates extracellular matrix-cell interactions in the second heart field
| Autor: | Claudio Cortes, Marchesa Bilio, Robert G. Kelly, Antonio Baldini, Alessandra Altomonte, Daniela Alfano |
|---|---|
| Přispěvatelé: | Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Telethon Institute for Genetics and Medicine, Telethon Institute, Alfano, D., Altomonte, A., Cortes, C., Bilio, M., Kelly, R. G., Baldini, A. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Organogenesis
[SDV]Life Sciences [q-bio] Cell Cell Communication Myoblasts Extracellular matrix Mice 0302 clinical medicine Cell Movement Myosin Cells Cultured Genetics (clinical) ComputingMilieux_MISCELLANEOUS Mice Knockout 0303 health sciences Heart development Chemistry 030302 biochemistry & molecular biology Cell Polarity Gene Expression Regulation Developmental Heart Cell migration Tbx1 Adhesion General Medicine Extracellular Matrix Cell biology medicine.anatomical_structure embryonic structures Signal transduction Signal Transduction TBX1 Cell signaling Integrin Morphogenesis Biology Focal adhesion 03 medical and health sciences stomatognathic system medicine Cell Adhesion Genetics Animals Cell adhesion Molecular Biology Paxillin 030304 developmental biology Focal Adhesions Mice Inbred C57BL biology.protein T-Box Domain Proteins 030217 neurology & neurosurgery |
| Zdroj: | Human Molecular Genetics Human Molecular Genetics, Oxford University Press (OUP), 2019, 28 (14), pp.2295-2308. ⟨10.1093/hmg/ddz058⟩ Human molecular genetics 28 (2019): 2295–2308. doi:10.1093/hmg/ddz058 info:cnr-pdr/source/autori:Alfano D.; Altomonte A.; Cortes C.; Bilio M.; Kelly R.G.; Baldini A./titolo:Tbx1 regulates extracellular matrix-cell interactions in the second heart field/doi:10.1093%2Fhmg%2Fddz058/rivista:Human molecular genetics (Print)/anno:2019/pagina_da:2295/pagina_a:2308/intervallo_pagine:2295–2308/volume:28 Human Molecular Genetics, 2019, 28 (14), pp.2295-2308. ⟨10.1093/hmg/ddz058⟩ |
| ISSN: | 0964-6906 1460-2083 |
| DOI: | 10.1093/hmg/ddz058⟩ |
| Popis: | SUMMARYTbx1,the major candidate gene for DiGeorge or 22q11.2 deletion syndrome, is required for efficient incorporation of cardiac progenitors (CPs) of the second heart field (SHF) into the heart. However, the mechanisms by which TBX1 regulates this process are still unclear. Here, we have used two independent models, mouse embryos and cultured cells, to define the role of TBX1 in establishing morphological and dynamic characteristics of SHF in the mouse. We found that loss of TBX1 impairs extra cellular matrix (ECM)-integrin-focal adhesion (FA) signaling in both models. Mosaic analysis in embryos showed that this function is non-cell autonomous and, in cultured cells, loss of TBX1 impairs cell migration and focal adhesions. Additionally, we found that ECM-mediated outside-in integrin signaling is disrupted upon loss of TBX1. Finally, we show that interfering with the ECM-integrin-FA axis between E8.5 and E9.5 in mouse embryos, corresponding to the time window within which TBX1 is required in the SHF, causes outflow tract dysmorphogenesis. Our results demonstrate that TBX1 is required to maintain the integrity of ECM-cell interactions in the SHF, and that this interaction is critical for cardiac outflow tract development. More broadly, our data identifies a novel TBX1 downstream pathway as an important player in SHF tissue architecture and cardiac morphogenesis. |
| Databáze: | OpenAIRE |
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