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Department of Physiology, Development and Neuroscience

Transcription factor HIF2a necessary for the development and function of the carotid body.

Study by Randall Johnson's lab uses genetic and physiological analysis to demonstrate the essential role of the transcription factor HIF-2alpha in the sympathetic nervous system control of the ventilatory response to hypoxia

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-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.

The image illustrates the presence of TH+ (tyrosine hydroxylase, green) and p-S6+ (phospho-ribosomal S6, red) proteins in developing carotid body glomus cells of wild-type mouse embryos (stage E18.5). The picture has been modified to emphasize the changes in gene expression.

Reference: 10.7554/eLife.34681