PREreview of A pre-vertebrate endodermal origin of calcitonin-producing neuroendocrine cells

Summary

In this study Rees et al, address the developmental origin of calcitonin-producing cells (C-cells) in a range of chordates with key phylogenetic positions. The authors focus on determining whether this cell type has a common developmental origin in chordates, which will support (by the parsimony principle) a common evolutionary origin. Using a combination of lineage tracing and calcitonin gene expression, the authors were able to trace the overall germ layer origin of C-cells in 5 species across the chordate phylogeny (birds, bony and cartilaginous fish, tunicates and amphioxus). The study’s main finding is that C-cells in all chordates analysed have a pharyngeal endodermal origin, including in chicks, a species where previous studies rather suggested a neural crest origin. The authors therefore conclude that this probably is due to a common evolutionary origin. Through seemingly simple, yet convincing experiments in a carefully selected set of species, this study provides compelling evidence for an evolutionarily conserved calcitonin-expressing cell type. The authors leveraged the most powerful tools available in each of the systems analysed to support their conclusions (e.g. genetic labelling of cell lineages in those species where this is possible). While this study provides an enticing evolutionary scenario, care in interpreting the implications of the results in evolutionary terms must be taken, in particular, the need for further markers to homologise calcitonin-expressing cells and the acknowledgment that common developmental origin does not always equate common evolutionary origin. These and other comments of this study are presented below.

Major issues

We did not find any major flaws in this study based on the results presented and the conclusions derived from them.

Minor issues

1. We suggest rephrasing parts of the discussion and the conclusion: The authors’ findings of “putative C-cells” in tunicates and amphioxus is very intriguing by itself. However, additional information such as ultrastructural and/or functional data (e.g. gene cascades within the cells, interactions with other cells, …) is needed to ascertain homology between the cells across chordates.  

2. We additionally suggest to opt for a more nuanced and active title that more accurately reflects the findings of the study (e.g. “Calcitonin-producing neuroendocrine cells in chordates have an endodermal origin” or “Calcitonin-producing cells of endodermal origin join the chordate neuroendocrine repertoire?”). In addition, we suggest that instead of using the term “pre-vertebrate”, the authors rather opt for a more phylogenetically balanced term.

3. We suggest including overview-images of the entire specimens to help the reader know where histological sections were taken from (as done in Figure 4c) . 

4. We suggest including the neural crest cell labelling experiments alongside the endodermal labelings wherever possible (e.g. the skate experiments are mentioned but not shown). In this manner, the findings will be further emphasised.

5.  We suggest the authors clarify why in some of the double staining images such as Figure 4f and g the signal of each label (e.g. Calca and CM-DiI) is not as clear as in the images of single labelling experiments. 

Concluding remarks

This study provides new insights into chordate C-cells development and evolution. It suggests a single and early origin of these cells. Since this study combines clearly phrased research questions and testable hypotheses with efficient, state-of-the-art-methods in well-chosen species, we recommend this study not only to readers working in the fields of neuroendocrine cell evolution or C-cells in vertebrates, but also to a broader audience interested in cell type evolution in animals.      

Competing Interests

The authors declare that they have no competing interests. 

Competing interests

The authors declare that they have no competing interests.