Diversification of heart progenitor cells by EGF signaling and differential modulation of ETS protein activity

Autor: Dominik Hollfelder, Ingolf Reim, Leonie Hartmann, Katharina Scharf, Benjamin Schwarz
Rok vydání: 2018
Předmět:
0301 basic medicine
Embryo
Nonmammalian
TBX20
Cell
Regulator
Animals
Genetically Modified
epidermal growth factor signaling
Gene expression
Myocyte
Biology (General)
Cells
Cultured
D. melanogaster
Heart development
Effector
Stem Cells
General Neuroscience
Gene Expression Regulation
Developmental
Heart
General Medicine
Anatomy
Cell biology
Drosophila melanogaster
medicine.anatomical_structure
Medicine
ETS transcription factors
SAM domain factors
Signal transduction
Stem cell
Research Article
Signal Transduction
QH301-705.5
Science
Biology
seven-up/COUP-TFII
T-box factors
General Biochemistry
Genetics and Molecular Biology
Proto-Oncogene Protein c-ets-1
03 medical and health sciences
medicine
Animals
cardiac cell specification
Progenitor cell
Gene
Transcription factor
Epidermal Growth Factor
General Immunology and Microbiology
030104 developmental biology
Developmental biology
Developmental Biology
Zdroj: eLife, Vol 7 (2018)
eLife
ISSN: 2050-084X
DOI: 10.7554/elife.32847
Popis: For coordinated circulation, vertebrate and invertebrate hearts require stereotyped arrangements of diverse cell populations. This study explores the process of cardiac cell diversification in the Drosophila heart, focusing on the two major cardioblast subpopulations: generic working myocardial cells and inflow valve-forming ostial cardioblasts. By screening a large collection of randomly induced mutants, we identified several genes involved in cardiac patterning. Further analysis revealed an unexpected, specific requirement of EGF signaling for the specification of generic cardioblasts and a subset of pericardial cells. We demonstrate that the Tbx20 ortholog Midline acts as a direct target of the EGFR effector Pointed to repress ostial fates. Furthermore, we identified Edl/Mae, an antagonist of the ETS factor Pointed, as a novel cardiac regulator crucial for ostial cardioblast specification. Combining these findings, we propose a regulatory model in which the balance between activation of Pointed and its inhibition by Edl controls cardioblast subtype-specific gene expression.
eLife digest Organs contain many different kinds of cells, each specialised to perform a particular role. The fruit fly heart, for example, has two types of muscle cells: generic heart muscle cells and ostial heart muscle cells. The generic cells contract to force blood around the body, whilst the ostial cells form openings that allow blood to enter the heart. Though both types of cells carry the same genetic information, each uses a different combination of active genes to perform their role. During development, the cells must decide whether to become generic or ostial. They obtain signals from other cells in and near the developing heart, and respond by turning genes on or off. The response uses proteins called transcription factors, which bind to regulatory portions of specific genes. The sequence of signals and transcription factors that control the fate of developing heart muscle cells was not known. So Schwarz et al. examined the process using a technique called a mutagenesis screen. This involved triggering random genetic mutations and looking for flies with defects in their heart muscle cells. Matching the defects to the mutations revealed genes responsible for heart development. Schwarz et al. found that for cells to develop into generic heart muscle cells, a signal called epidermal growth factor (EGF) switches on a transcription factor called Pointed in the cells. Pointed then turns on another transcription factor that switches off the genes for ostial cells. Conversely, ostial heart muscle cells develop when a protein called ‘ETS-domain lacking’ (Edl) interferes with Pointed, allowing the ostial genes to remain on. The balance between Pointed and Edl controls which type of heart cell each cell will become. Many cells in other tissues in fruit flies also produce the Pointed and Edl proteins and respond to EGF signals. This means that this system may help to decide the fate of cells in other organs. The EGF signaling system is also present in other animals, including humans. Future work could reveal whether the same molecular decision making happens in our own hearts.
Databáze: OpenAIRE
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