title: Tissue factor pathway inhibitor-2 is critical in zebrafish cardiogenesis.
abstract: Human tissue factor pathway inhibitor-2 (Tfpi-2) is an extracellular matrix-associated Kunitz-type serine proteinase inhibitor and plays an important role in various cellular processes. We have previously shown that zebrafish Tfpi-2 (zTfpi-2) mainly expressed in the brain and heart of zebrafish, and it is involved in the development of central nervous system. Here, we identified zTfpi-2 as an evolutionarily conserved protein essential for zebrafish heart development, as embryos depleted of zTfpi-2 failed to undergo cardiogenesis. Changes of cardiogenic markers, vmhc, amhc and bmp4, confirmed zTfpi-2 knockdown caused cardiac defects, including retrenched ventricle, enlarged atrium and malformation of atrioventricular boundary. The sarcomeric organization was also disrupted by embryonic depletion of zTfpi-2, thus establishing the functional role of zTfpi-2 in cardiac contractility. In addition, hematopoietic defects were detected in the zTfpi-2-deficiency embryos. Importantly, injection of ztfpi-2 mRNA attenuated those cardiac and hematopoietic defects. Taken together, this study demonstrated a critical role of zTfpi-2 during embryonic cardiac development, as well as an important regulator of hematopoiesis.
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Children's Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Danping
authors.initials: D
authors.lastname: Wen
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Children's Hospital, Fudan University, Shanghai 200032, China. Electronic address: duanma@shmu.edu.cn.
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D053858:Metabolic Networks and Pathways; D038081:Organogenesis / Q000235:genetics / Q000502:physiology*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology / Q000648:ultrastructure; D015027:Zebrafish / Q000097:blood / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D006023:Glycoproteins; D053491:Proteinase Inhibitory Proteins, Secretory; D029961:Zebrafish Proteins; C000596118:tfpi2 protein, zebrafish; C021240:tissue-factor-pathway inhibitor 2
keywords: Cardiac development; Notch pathway; Tfpi-2; Zebrafish