Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published February 20, 2024 | Published
Journal Article Open

Sea lamprey enlightens the origin of the coupling of retinoic acid signaling to vertebrate hindbrain segmentation


Retinoic acid (RA) is involved in antero-posterior patterning of the chordate body axis and, in jawed vertebrates, has been shown to play a major role at multiple levels of the gene regulatory network (GRN) regulating hindbrain segmentation. Knowing when and how RA became coupled to the core hindbrain GRN is important for understanding how ancient signaling pathways and patterning genes can evolve and generate diversity. Hence, we investigated the link between RA signaling and hindbrain segmentation in the sea lamprey Petromyzon marinus, an important jawless vertebrate model providing clues to decipher ancestral vertebrate features. Combining genomics, gene expression, and functional analyses of major components involved in RA synthesis (Aldh1as) and degradation (Cyp26s), we demonstrate that RA signaling is coupled to hindbrain segmentation in lamprey. Thus, the link between RA signaling and hindbrain segmentation is a pan vertebrate feature of the hindbrain and likely evolved at the base of vertebrates.

Copyright and License

© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.


We thank Brian Slaughter and Ruth Williams for providing guidance on generating and visualizing HCR data, Stephen Green, Megan Martik, and Tetsuto Miyashita for assistance with lamprey husbandry, and members of the Krumlauf laboratory for feedback on the experiments and manuscript. This study was conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the NIH and protocols approved by the Institutional Animal Care and Use Committees of the California Institute of Technology (lamprey, MEB Protocol: #IA23-1436). This work was supported by a grant from the Stowers Institute for Medical Research to R.K. (grant #1001) and by a grant to M.E.B. (R35NS111564). This work was conducted to fulfill, in part, the requirements for A.M.H.B.’s thesis research as a Ph.D. student registered with the Open University, and we would like to thank the thesis committee members (Paul Trainor, Tatjana Piotrowski and Brian Slaughter) for their insightful comments and feedback.


A.M.H.B., H.J.P., M.E.B. and R.K. conceived this research program. A.M.H.B. and H.J.P. conducted the experiments and performed lamprey husbandry. A.J.P generated the RNAseq graph and J.A.M. contributed to optimizing the HCR protocol and generating HCR data. A.M.H.B., H.J.P., M.E.B. and R.K. analyzed the data, discussed the ideas and interpretations, and wrote the manuscript.

Data Availability

The authors declare that all data supporting the findings of this study are available within the article and its supplementary information files or from the corresponding author upon reasonable request. Original data underlying this manuscript can be accessed from the Stowers Original Data Repository at http://www.stowers.org/research/publications/libpb-2405.

Conflict of Interest

The authors declare no competing interests.


Files (14.3 MB)
Name Size Download all
5.7 MB Preview Download
8.6 MB Preview Download

Additional details

February 21, 2024
February 28, 2024