HIF-1α is required for development of the sympathetic nervous system

Romana Bohuslavova, Radka Cerychova, Frantisek Papousek, Veronika Olejnickova, Martin Bartos, Agnes Görlach, Frantisek Kolar, David Sedmera, Gregg L. Semenza, Gabriela Pavlinkova

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)13414-13423
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number27
DOIs
StatePublished - Jan 1 2019

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Keywords

  • Cardiac innervation
  • Coronary artery branching
  • Hypoxia
  • Sympathetic neurons
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • General

Cite this

Bohuslavova, R., Cerychova, R., Papousek, F., Olejnickova, V., Bartos, M., Görlach, A., Kolar, F., Sedmera, D., Semenza, G. L., & 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), 13414-13423. https://doi.org/10.1073/pnas.1903510116