LampRA: A Study of the Evolution of the Retinoic Acid Signalling Pathway and Its Coupling to Vertebrate Hindbrain Segmentation Using the Sea Lamprey Petromyzon marinus

Bedois, Alice M. H. (2023). LampRA: A Study of the Evolution of the Retinoic Acid Signalling Pathway and Its Coupling to Vertebrate Hindbrain Segmentation Using the Sea Lamprey Petromyzon marinus. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.00015481

Abstract

A major feature differentiating vertebrates from other chordates is the establishment of a complex brain as part of the central nervous system. The hindbrain is a conserved and unique structure of the developing vertebrate brain, which is temporarily subdivided into 7 segments, an important process that influences craniofacial patterning and neurogenesis. Hindbrain segmentation is governed by a complex gene regulatory network (GRN). Retinoic Acid (RA) plays a major role at multiple levels of the GRN to regulate segmentation genes, including Hox genes. While major components of the RA machinery can be traced back to the deuterostome ancestor, the RA/Hox hierarchy and its role in axial patterning only emerged in chordates and was later co-opted in the hindbrain GRN during the evolution of vertebrates. Previous studies concluded that RA only played a minor role in hindbrain segmentation in lamprey, a jawless vertebrate model, therefore questioning the evolutionary origin of the input of this signalling pathway into the vertebrate hindbrain GRN.

We have addressed this question by investigating the spatio-temporal deployment of key components of the RA machinery in sea lamprey Petromyzon marinus, and by disrupting them through pharmacological treatments and CRISPR/Cas9 technology. Our results indicate that RA plays a globally conserved role in the GRN for hindbrain segmentation in lamprey. Hence, the coupling of the RA signalling pathway to hindbrain segmentation during the evolution of vertebrates emerged earlier than previously inferred. Following this, we are currently investigating major events that may have occurred in the evolution of the RA machinery in chordates while also looking into the evolution of RA-responsive enhancers in the hindbrain GRN. Our results illustrate the utility of sea lamprey as a model for understanding the origin and evolution of vertebrate traits and for delineating evolutionary events that led to the emergence of jawed vertebrates.

Viewing alternatives

Metrics

Item Actions

Export

You can export this page using these formats Digital Object Identifier - DOI