PT  - JOURNAL ARTICLE
AU  - David Macías
AU  - Andrew S. Cowburn
AU  - Hortensia Torres-Torrelo
AU  - Patricia Ortega-Sáenz
AU  - José López-Barneo
AU  - Randall S. Johnson
TI  - HIF-2α is essential for carotid body development and function
AID  - 10.1101/250928
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 250928
4099  - http://biorxiv.org/content/early/2018/01/19/250928.short
4100  - http://biorxiv.org/content/early/2018/01/19/250928.full
AB  - 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-2a, 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-2a in carotid body development, growth and function.