Evolutionary Developmental Biology: Sensing oxygen inside and out
Neuroendocrine cells act as oxygen sensors in animals from fish to humans, but the evolutionary origins of these cells are only just becoming clear.
- Columbia University Medical Center, United States
For single-celled organisms like bacteria, every cell can detect changes in the level of oxygen in its environment and respond accordingly. Things, however, can be rather more complicated in multicellular organisms (Jonz et al., 2016). For example, animals must have a respiratory system to deliver enough oxygen to millions of cells to meet with their metabolic demands. An animal’s survival also depends on it monitoring oxygen levels both internally (for example, in its blood) and externally (in the environment). Multicellular organisms have oxygen sensors that consist largely of cells called neuroendocrine cells. When oxygen levels drop, these sensors release neurotransmitters, chemicals that excite nearby neurons to signal to a control center in the brain. The control center then triggers reflexes that increase the frequency of breathing.
These oxygen sensors have evolved at strategic places in the body. In land animals like mammals and birds (collectively referred to as amniotes), these sensors are found in two distinct locations: next to the carotid arteries, and in the airways of the lungs. The carotid arteries are the major blood vessels that deliver oxygenated blood to the head and neck, and the neuroendocrine cells are packed closely together to form a structure called the carotid body located where these arteries branch. In the airways of the lungs, the oxygen sensors are distributed as single cells or in small groups known as neuroendocrine bodies, present mostly at the branch-points. Primarily aquatic species, like fish and amphibians (collectively referred to as non-amniotes), have oxygen-sensing neuroendocrine cells in their gills to detect oxygen in the water. At least one fish, the jawless lamprey, also has oxygen-sensitive cells that are rich in neurotransmitters near its major blood vessels, reminiscent of the carotid body found in the land animals (Jonz et al., 2016).
The multiple similarities of neuroendocrine cells in these different structures have led to a long-lasting debate as to how they are related in terms of evolution, particularly whether the neuroendocrine cells in the carotid body and the lungs of land animals evolved from the neuroendocrine cells in the gills of their aquatic ancestors. Now, in eLife, Clare Baker at the University of Cambridge and colleagues – including Dorit Hockman as first author – address this controversy and report that these different oxygen sensors diverged long before animals transitioned onto land (Hockman et al., 2017).
Previous studies in mice and birds had already shown that lung neuroendocrine cells have a different embryonic origin than those found in the carotid body. Most animal embryos form three distinct layers during the early stages of development: endoderm, mesoderm and ectoderm. These layers later contribute to different parts of the body. The neuroendocrine cells in the lung develop from the endoderm, while those in the carotid body develop from the neural crest, which arises from the ectoderm (Pearse et al., 1973; Hoyt et al., 1990; Song et al., 2012; Kuo and Krasnow, 2015).
To decipher the evolutionary relationships between the oxygen sensors, Hockman et al. – who are based at institutions in Germany, Ireland, the Netherlands, the US and the UK – set out to determine the origin of the gill neuroendocrine cells. To do this, they traced how neuroendocrine cells develop in the embryos of three non-amniotes: namely two species of fish (lamprey and zebrafish) and one species of frog (Xenopus). First, they engineered zebrafish so that all cells derived from the neural crest would fluoresce red. However, no red cells were seen in the gills, which indicated that gill neuroendocrine cells are not neural crest-derived. The finding that zebrafish mutants which lack neural crest cells still developed neuroendocrine cells in their gills further supported this conclusion. Importantly, Hockman et al. went on to confirm that the neuroendocrine cells in the zebrafish gills develop from endodermal cells, just like those in the lungs of mice. Similar results were seen with lamprey and Xenopus.
The finding that during development neuroendocrine cells in gills arise from the endoderm and not the neural crest effectively ruled out the possibility that they could have evolved from the same precursor cell as carotid body cells. Hockman et al. then identified neural crest-derived cells rich in neurotransmitters near major blood vessels in young lamprey and zebrafish. Specifically, these cells were found near large blood vessels of the fish’s pharyngeal arches, an association that closely resembles that seen in the carotid bodies of land animals. This led Hockman et al. to propose a new model for the evolution of oxygen sensors (Figure 1). According to this model, the carotid body seen in amniotes evolved from the grouping together of the neural crest-derived cells that were present near the pharyngeal arches of non-amniotes (which eventually develop into the gill arches). Later, these cells altered the neurotransmitters that they produced, and became wired into the nervous system. By contrast, the neuroendocrine cells in the gills and lungs continued to develop in situ from endodermal cells when animals transitioned from an aquatic to a terrestrial life.
Figure 1
A new model for the evolution of oxygen sensors.
Oxygen-sensitive neuroendocrine (NE) cells (yellow) associated with blood vessels (red) serve as sensors for internal oxygen levels (top). These include catecholaminergic cells in an ancestral structure in non-amniotes like fish (left), and the glomus cells in the carotid body of amniotes like humans (right). Other neuroendocrine cells act as sensors for external oxygen (bottom). These include cells in the gills of fish (left) and the airways of amniotes (right). Hockman et al. propose that the clusters of catecholaminergic cells near the blood vessels in non-amniotes evolved into the carotid bodies of amniotes. The neuroendocrine cells in these internal sensors are all derived from the neural crest. By contrast, the external oxygen sensors in gills and airways are derived from the endoderm in both non-amniotes and amniotes. Neurons are shown in blue; accessory cells are shown in gray. NEB: neuroendocrine body.
The challenge ahead is to elucidate the network of genes that led oxygen-sensing structures to diversify as animals evolved. Some of the signals needed for neuroendocrine cells to develop are already known (Borges et al., 1997; Ito et al., 2000; Kameda, 2005; Tsao et al., 2009; Branchfield et al., 2016). However, there is evidence that each type of sensor requires slightly different cues and produces a different combination of molecules (Dauger et al., 2003). Additional knowledge of these differences will help us to understand how these sensors acquired their specialized functions to fulfill new roles during evolution.
References
-
Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epitheliumDevelopment 127:3913–3921.
-
Sensing and surviving hypoxia in vertebratesAnnals of the New York Academy of Sciences 1365:43–58.https://doi.org/10.1111/nyas.12780
-
Mash1 is required for glomus cell formation in the mouse carotid bodyDevelopmental Biology 283:128–139.https://doi.org/10.1016/j.ydbio.2005.04.004
Article and author information
Author details
Wellington V Cardoso
Publication history
Copyright
© 2017, Stupnikov et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Evolutionary Developmental Biology: Sensing oxygen inside and out
eLife 6:e27467.
https://doi.org/10.7554/eLife.27467
Further reading
-
- Developmental Biology
- Stem Cells and Regenerative Medicine
In holothurians, the regenerative process following evisceration involves the development of a ‘rudiment’ or ‘anlage’ at the injured end of the mesentery. This regenerating anlage plays a pivotal role in the formation of a new intestine. Despite its significance, our understanding of the molecular characteristics inherent to the constituent cells of this structure has remained limited. To address this gap, we employed state-of-the-art scRNA-seq and hybridization chain reaction fluorescent in situ hybridization analyses to discern the distinct cellular populations associated with the regeneration anlage. Through this approach, we successfully identified 13 distinct cell clusters. Among these, two clusters exhibit characteristics consistent with putative mesenchymal cells, while another four show features akin to coelomocyte cell populations. The remaining seven cell clusters collectively form a large group encompassing the coelomic epithelium of the regenerating anlage and mesentery. Within this large group of clusters, we recognized previously documented cell populations such as muscle precursors, neuroepithelial cells, and actively proliferating cells. Strikingly, our analysis provides data for identifying at least four other cellular populations that we define as the precursor cells of the growing anlage. Consequently, our findings strengthen the hypothesis that the coelomic epithelium of the anlage is a pluripotent tissue that gives rise to diverse cell types of the regenerating intestinal organ. Moreover, our results provide the initial view into the transcriptomic analysis of cell populations responsible for the amazing regenerative capabilities of echinoderms.
-
- Cell Biology
- Developmental Biology
The rete ovarii (RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Gray’s Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the mouse ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow toward the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.
