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Isolation and Characterization of Single Cells from Zebrafish Embryos
Published on: March 12, 2016
Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective heart morphogenesis in mice and zebrafish
Stamatiki Katraki-Pavlou1,2, Pinelopi Kastana1, Dimitris Bousis1
1Laboratory of Molecular Pharmacology, Department of Pharmacy, School of Health Sciences, University of Patras, Patras, Greece.
Abstract:
Protein tyrosine phosphatase receptor-ζ1 (PTPRZ1) is a transmembrane tyrosine phosphatase receptor highly expressed in embryonic stem cells. In the present work, gene expression analyses of Ptprz1-/- and Ptprz1+/+ mice endothelial cells and hearts pointed to an unidentified role of PTPRZ1 in heart development through the regulation of heart-specific transcription factor genes. Echocardiography analysis in mice identified that both systolic and diastolic functions are affected in Ptprz1-/- compared with Ptprz1+/+ hearts, based on a dilated left ventricular (LV) cavity, decreased ejection fraction and fraction shortening, and increased angiogenesis in Ptprz1-/- hearts, with no signs of cardiac hypertrophy. A zebrafish ptprz1-/- knockout was also generated and exhibited misregulated expression of developmental cardiac markers, bradycardia, and defective heart morphogenesis characterized by enlarged ventricles and defected contractility. A selective PTPRZ1 tyrosine phosphatase inhibitor affected zebrafish heart development and function in a way like what is observed in the ptprz1-/- zebrafish. The same inhibitor had no effect in the function of the adult zebrafish heart, suggesting that PTPRZ1 is not important for the adult heart function, in line with data from the human cell atlas showing very low to negligible PTPRZ1 expression in the adult human heart. However, in line with the animal models, Ptprz1 was expressed in many different cell types in the human fetal heart, such as valvar, fibroblast-like, cardiomyocytes, and endothelial cells. Collectively, these data suggest that PTPRZ1 regulates cardiac morphogenesis in a way that subsequently affects heart function and warrant further studies for the involvement of PTPRZ1 in idiopathic congenital cardiac pathologies.NEW & NOTEWORTHY Protein tyrosine phosphatase receptor ζ1 (PTPRZ1) is expressed in fetal but not adult heart and seems to affect heart development. In both mouse and zebrafish animal models, loss of PTPRZ1 results in dilated left ventricle cavity, decreased ejection fraction, and fraction shortening, with no signs of cardiac hypertrophy. PTPRZ1 also seems to be involved in atrioventricular canal specification, outflow tract morphogenesis, and heart angiogenesis. These results suggest that PTPRZ1 plays a role in heart development and support the hypothesis that it may be involved in congenital cardiac pathologies.
Insights
Protein tyrosine phosphatase receptor ζ1 (PTPRZ1) is crucial for fetal heart development, impacting cardiac morphogenesis and function. Loss of PTPRZ1 in animal models leads to heart defects, suggesting its role in congenital cardiac pathologies.
Area of Science:
- Developmental Biology
- Cardiovascular Research
- Molecular Cardiology
Background:
- Protein tyrosine phosphatase receptor ζ1 (PTPRZ1) is a transmembrane receptor tyrosine phosphatase.
- PTPRZ1 is highly expressed in embryonic stem cells and fetal heart tissues.
- Its role in heart development was previously unidentified.
Purpose of the Study:
- To investigate the role of PTPRZ1 in heart development and function.
- To analyze the impact of PTPRZ1 deficiency on cardiac morphogenesis and contractility.
- To explore the potential involvement of PTPRZ1 in congenital cardiac pathologies.
Main Methods:
- Gene expression analysis in PTPRZ1 knockout (Ptprz1-/-) and wild-type (Ptprz1+/+) mice.
- Echocardiography to assess cardiac function in knockout and wild-type mice.
- Generation and analysis of a zebrafish ptprz1-/- knockout model.
- Pharmacological inhibition of PTPRZ1 in zebrafish.
Main Results:
- PTPRZ1 deficiency in mice resulted in dilated left ventricle, decreased ejection fraction, and impaired systolic/diastolic function without hypertrophy.
- Zebrafish ptprz1-/- mutants exhibited cardiac developmental defects, including enlarged ventricles and reduced contractility.
- PTPRZ1 inhibition affected zebrafish heart development similarly to knockout models, but not adult heart function.
- PTPRZ1 expression is high in the fetal human heart but negligible in the adult heart.
Conclusions:
- PTPRZ1 plays a significant role in regulating cardiac morphogenesis and function during fetal development.
- Loss of PTPRZ1 function leads to specific cardiac abnormalities observed in both mouse and zebrafish models.
- PTPRZ1 is a potential candidate for involvement in idiopathic congenital cardiac pathologies.
