Tags

Type your tag names separated by a space and hit enter

HIF-1α is required for development of the sympathetic nervous system.
Proc Natl Acad Sci U S A 2019; 116(27):13414-13423PN

Abstract

The molecular mechanisms regulating sympathetic innervation of the heart during embryogenesis and its importance for cardiac development and function remain to be fully elucidated. We generated mice in which conditional knockout (CKO) of the Hif1a gene encoding the transcription factor hypoxia-inducible factor 1α (HIF-1α) is mediated by an Islet1-Cre transgene expressed in the cardiac outflow tract, right ventricle and atrium, pharyngeal mesoderm, peripheral neurons, and hindlimbs. These Hif1aCKO mice demonstrate significantly decreased perinatal survival and impaired left ventricular function. The absence of HIF-1α impaired the survival and proliferation of preganglionic and postganglionic neurons of the sympathetic system, respectively. These defects resulted in hypoplasia of the sympathetic ganglion chain and decreased sympathetic innervation of the Hif1aCKO heart, which was associated with decreased cardiac contractility. The number of chromaffin cells in the adrenal medulla was also decreased, indicating a broad dependence on HIF-1α for development of the sympathetic nervous system.

Authors+Show Affiliations

Laboratory of Molecular Pathogenetics, Institute of Biotechnology, Czech Academy of Sciences, 252 50 Vestec, Czechia; romana.bohuslavova@ibt.cas.cz gsemenza@jhmi.edu gpavlinkova@ibt.cas.cz.Laboratory of Molecular Pathogenetics, Institute of Biotechnology, Czech Academy of Sciences, 252 50 Vestec, Czechia.Institute of Physiology, Czech Academy of Sciences, 142 00 Prague, Czechia.Institute of Physiology, Czech Academy of Sciences, 142 00 Prague, Czechia. Institute of Anatomy, First Faculty of Medicine, Charles University, 110 00 Prague, Czechia.Institute of Anatomy, First Faculty of Medicine, Charles University, 110 00 Prague, Czechia. Institute of Dental Medicine, First Faculty of Medicine, Charles University, 110 00 Prague, Czechia.German Heart Centre Munich, Technical University, 80636 Munich, Germany. German Centre for Cardiovascular Research, Partner Site Munich, Munich Heart Alliance, 80636 Munich, Germany.Institute of Physiology, Czech Academy of Sciences, 142 00 Prague, Czechia.Institute of Physiology, Czech Academy of Sciences, 142 00 Prague, Czechia. Institute of Anatomy, First Faculty of Medicine, Charles University, 110 00 Prague, Czechia.McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205; romana.bohuslavova@ibt.cas.cz gsemenza@jhmi.edu gpavlinkova@ibt.cas.cz. Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.Laboratory of Molecular Pathogenetics, Institute of Biotechnology, Czech Academy of Sciences, 252 50 Vestec, Czechia; romana.bohuslavova@ibt.cas.cz gsemenza@jhmi.edu gpavlinkova@ibt.cas.cz.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31196952

Citation

Bohuslavova, Romana, et al. "HIF-1α Is Required for Development of the Sympathetic Nervous System." Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 27, 2019, pp. 13414-13423.
Bohuslavova R, Cerychova R, Papousek F, et al. HIF-1α is required for development of the sympathetic nervous system. Proc Natl Acad Sci USA. 2019;116(27):13414-13423.
Bohuslavova, R., Cerychova, R., Papousek, F., Olejnickova, V., Bartos, M., Görlach, A., ... Pavlinkova, G. (2019). HIF-1α is required for development of the sympathetic nervous system. Proceedings of the National Academy of Sciences of the United States of America, 116(27), pp. 13414-13423. doi:10.1073/pnas.1903510116.
Bohuslavova R, et al. HIF-1α Is Required for Development of the Sympathetic Nervous System. Proc Natl Acad Sci USA. 2019 Jul 2;116(27):13414-13423. PubMed PMID: 31196952.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HIF-1α is required for development of the sympathetic nervous system. AU - Bohuslavova,Romana, AU - Cerychova,Radka, AU - Papousek,Frantisek, AU - Olejnickova,Veronika, AU - Bartos,Martin, AU - Görlach,Agnes, AU - Kolar,Frantisek, AU - Sedmera,David, AU - Semenza,Gregg L, AU - Pavlinkova,Gabriela, Y1 - 2019/06/13/ PY - 2019/6/15/pubmed PY - 2019/6/15/medline PY - 2019/6/15/entrez KW - cardiac innervation KW - coronary artery branching KW - hypoxia KW - sympathetic neurons KW - tyrosine hydroxylase SP - 13414 EP - 13423 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 116 IS - 27 N2 - The molecular mechanisms regulating sympathetic innervation of the heart during embryogenesis and its importance for cardiac development and function remain to be fully elucidated. We generated mice in which conditional knockout (CKO) of the Hif1a gene encoding the transcription factor hypoxia-inducible factor 1α (HIF-1α) is mediated by an Islet1-Cre transgene expressed in the cardiac outflow tract, right ventricle and atrium, pharyngeal mesoderm, peripheral neurons, and hindlimbs. These Hif1aCKO mice demonstrate significantly decreased perinatal survival and impaired left ventricular function. The absence of HIF-1α impaired the survival and proliferation of preganglionic and postganglionic neurons of the sympathetic system, respectively. These defects resulted in hypoplasia of the sympathetic ganglion chain and decreased sympathetic innervation of the Hif1aCKO heart, which was associated with decreased cardiac contractility. The number of chromaffin cells in the adrenal medulla was also decreased, indicating a broad dependence on HIF-1α for development of the sympathetic nervous system. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/31196952/HIF-1α_is_required_for_development_of_the_sympathetic_nervous_system L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=31196952 DB - PRIME DP - Unbound Medicine ER -