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Elife. 2018 Apr 19;7. pii: e34681. doi: 10.7554/eLife.34681.

HIF-2α is essential for carotid body development and function.

Author information

1
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
2
Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
3
Instituto de Biomedicina de Sevilla, Seville, Spain.
4
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.

Abstract

Mammalian adaptation to oxygen flux occurs at many levels, from shifts in cellular metabolism to physiological adaptations facilitated by the sympathetic nervous system and carotid body (CB). Interactions between differing forms of adaptive response to hypoxia, including transcriptional responses orchestrated by the Hypoxia Inducible transcription Factors (HIFs), are complex and clearly synergistic. We show here that there is an absolute developmental requirement for HIF-2α, one of the HIF isoforms, for growth and survival of oxygen sensitive glomus cells of the carotid body. The loss of these cells renders mice incapable of ventilatory responses to hypoxia, and this has striking effects on processes as diverse as arterial pressure regulation, exercise performance, and glucose homeostasis. We show that the expansion of the glomus cells is correlated with mTORC1 activation, and is functionally inhibited by rapamycin treatment. These findings demonstrate the central role played by HIF-2α in carotid body development, growth and function.

KEYWORDS:

carotid body; computational biology; hypoxia; mouse; sympathetic nerves; systems biology

PMID:
29671738
PMCID:
PMC5916566
DOI:
10.7554/eLife.34681
[Indexed for MEDLINE]
Free PMC Article

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