The Spatiotemporal Expression of Notch1 and Numb and Their Functional Interaction during Cardiac Morphogenesis
| Autor: | Hala Y. Abdelnasser, Bin Zhou, Mingfu Wu, Sayantap Datta, Yangyang Lu, Anika Nusrat, Lianjie Miao, Robert J. Schwartz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
QH301-705.5 Organogenesis Morphogenesis Notch signaling pathway Nerve Tissue Proteins Cell fate determination Biology cardiac progenitor cell differentiation Article Mice numb family proteins Animals Receptor Notch1 Progenitor cell outflow tract Biology (General) Gene knockout Myocardium Stem Cells Membrane Proteins Cell Differentiation Heart General Medicine Phenotype Embryonic stem cell notch signaling Cell biology cardiomyocyte proliferation embryonic structures NUMB cardiovascular system Female sense organs Signal Transduction |
| Zdroj: | Cells, Vol 10, Iss 2192, p 2192 (2021) Cells Volume 10 Issue 9 |
| ISSN: | 2073-4409 |
| Popis: | Numb family proteins (NFPs), including Numb and Numblike (Numbl), are commonly known for their role as cell fate determinants for multiple types of progenitor cells, mainly due to their function as Notch inhibitors. Previous studies have shown that myocardial NFP double knockout (MDKO) hearts display an up-regulated Notch activation and various defects in cardiac progenitor cell differentiation and cardiac morphogenesis. Whether enhanced Notch activation causes these defects in MDKO is not fully clear. To answer the question, we examined the spatiotemporal patterns of Notch1 expression, Notch activation, and Numb expression in the murine embryonic hearts using multiple approaches including RNAScope, and Numb and Notch reporter mouse lines. To further interrogate the interaction between NFPs and Notch signaling activation, we deleted both Notch1 or RBPJk alleles in the MDKO. We examined and compared the phenotypes of Notch1 knockout, NFPs double knockout, Notch1 Numb Numbl and RBPJk Numbl triple knockouts. Our study showed that Notch1 is expressed and activated in the myocardium at several stages, and Numb is enriched in the epicardium and did not show the asymmetric distribution in the myocardium. Cardiac-specific Notch1 deletion causes multiple structural defects and embryonic lethality. Notch1 or RBPJk deletion in MDKO did not rescue the structural defects in the MDKO but partially rescued the defects of cardiac progenitor cell differentiation, cardiomyocyte proliferation, and trabecular morphogenesis. Our study concludes that NFPs regulate progenitor cell differentiation, cardiomyocyte proliferation, and trabecular morphogenesis partially through Notch1 and play more roles than inhibiting Notch1 signaling during cardiac morphogenesis. |
| Databáze: | OpenAIRE |
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