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HIF-1 alpha is required for development of the sympathetic nervous system
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SYSNO ASEP 0507766 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title HIF-1 alpha is required for development of the sympathetic nervous system Author(s) Bohuslavová, Romana (BTO-N) RID
Čerychová, Radka (BTO-N)
Papoušek, František (FGU-C)
Olejníčková, Veronika (FGU-C) RID, ORCID, SAI
Bartoš, M. (CZ)
Goerlach, A. (DE)
Kolář, František (FGU-C) RID, ORCID, SAI
Sedmera, David (FGU-C) RID, ORCID, SAI
Semenza, G.L. (US)
Pavlínková, Gabriela (BTO-N) RID, ORCIDNumber of authors 10 Source Title Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences - ISSN 0027-8424
Roč. 116, č. 27 (2019), s. 13414-13423Number of pages 10 s. Language eng - English Country US - United States Keywords sympathetic neurons ; tyrosine hydroxylase ; cardiac innervation Subject RIV FH - Neurology OECD category Cardiac and Cardiovascular systems Subject RIV - cooperation Institute of Physiology - Cardiovascular Diseases incl. Cardiotharic Surgery R&D Projects GA17-04719S GA ČR - Czech Science Foundation (CSF) GA19-07378S GA ČR - Czech Science Foundation (CSF) LTC17023 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015062 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Research Infrastructure Czech-BioImaging - 90062 - Ústav molekulární genetiky AV ČR, v. v. i. Method of publishing Open access Institutional support BTO-N - RVO:86652036 ; FGU-C - RVO:67985823 UT WOS 000473427900043 EID SCOPUS 85068259608 DOI 10.1073/pnas.1903510116 Annotation 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 1 alpha (HIF-1 alpha) 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-1 alpha 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-1 alpha for development of the sympathetic nervous system. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2020 Electronic address https://doi.org/10.1073/pnas.1903510116
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