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Department of Physiology, Development and Neuroscience

Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes

New research by Clare Baker lab published on eLife sheds light on the evolution of carotid body cells

One focus of Clare Baker’s lab has been the evolution of the oxygen-sensitive cells of the carotid bodies. The carotid bodies are the small glands found on either side of our necks, near the carotid artery.  When the oxygen levels in our blood drop, such as at high altitudes, these specialised cells signal to the brain to activate hyperventilation and increase our heart rate. As a result, more oxygen is delivered to our cells. The carotid bodies are often compared to similar oxygen-sensitive cells found in fish gills, known as neuroepithelial cells. In fish, these cells detect changes in the oxygen levels in the surrounding water and in their blood. It has been suggested that when the ancestral vertebrates moved from the oceans onto land, the neuroepithelial cells found in the gills gave rise to the oxygen-sensing cells of the carotid bodies.

"If oxygen-sensitive carotid body cells evolved from ancestral fish neuroepithelial cells, we would expect them to develop from the same embryonic cell population" says Clare Baker. "The carotid body develops from ‘neural crest’ cells, which give rise to many tissues, including nerve cells. We asked if neuroepithelial cells are also neural crest-derived".

 As an embryo, this tadpole received a neural crest tissue graft on its right side from a Green Fluorescent Protein transgenic donor embryo. As a result, the neural crest-derived structures, such as the jaws,

The research team labelled neural crest cells in lamprey, zebrafish and frog embryos, using techniques such as injection with fluorescent dye or genetic modification so the neural crest cells produce fluorescent proteins. "To our surprise, the fluorescent dyes/proteins never labelled the neuroepithelial cells in the gills" says Baker. "Instead, these cells originated directly from the lining of the mouth and gills. Furthermore, their patterns of gene activity were different from the carotid body. We concluded that the carotid body did not evolve from ancestral fish neuroepithelial cells. Instead, we suggest that the neuroepithelial cells are related to oxygen-sensitive cells in the lungs.".

"It is important to know the evolutionary origins of carotid body cells in order to understand the evolutionary transition in the vertebrate lineage from an aquatic (water-breathing) to a fully terrestrial, obligate air-breathing life-style.”

The lead author of the paper, Dorit Hockman (currently a post-doctoral fellow at the University of Oxford and the University of Cape Town), said that, “During our study, we discovered some neural crest-derived cells associated with blood vessels in the gill region of zebrafish that we speculate could share an evolutionary ancestor with the carotid body of land-living vertebrates. A key challenge for testing this new hypothesis is to determine whether or not these cells are indeed oxygen-sensitive.

This research was funded in the Baker lab by the Wellcome Trust (4-year PhD studentship to Dorit Hockman). Funding to collaborating labs was primarily from the NIH.

Reference:  eLife 2017;10.7554/eLife.21231