In the study, Investigator and Scientific Director Robb Krumlauf, Ph.D. and colleagues show that the sea lamprey Petromyzon marinus, a survivor of ancient jawless vertebrates, exhibits a pattern of gene expression that is reminiscent of its jawed cousins, who evolved much, much later. Those genes, called Hox genes, function like a molecular ruler, determining where along the anterior-posterior (AP) axis an animal will place a particular feature or appendage. The new study means that that the genetic program used by jawed vertebrates, including fish, mice, and us, was up and running ages before a vertebrate ever possessed a recognizable face.
Here’s the abstract:
A defining feature governing head patterning of jawed vertebrates is a highly conserved gene regulatory network that integrates hindbrain segmentation with segmentally restricted domains of Hox gene expression. Although non-vertebrate chordates display nested domains of axial Hox expression, they lack hindbrain segmentation. The sea lamprey, a jawless fish, can provide unique insights into vertebrate origins owing to its phylogenetic position at the base of the vertebrate tree1, 2, 3. It has been suggested that lamprey may represent an intermediate state where nested Hox expression has not been coupled to the process of hindbrain segmentation4, 5, 6. However, little is known about the regulatory network underlying Hox expression in lamprey or its relationship to hindbrain segmentation. Here, using a novel tool that allows cross-species comparisons of regulatory elements between jawed and jawless vertebrates, we report deep conservation of both upstream regulators and segmental activity of enhancer elements across these distant species. Regulatory regions from diverse gnathostomes drive segmental reporter expression in the lamprey hindbrain and require the same transcriptional inputs (for example, Kreisler (also known as Mafba), Krox20 (also known as Egr2a)) in both lamprey and zebrafish. We find that lamprey hox genes display dynamic segmentally restricted domains of expression; we also isolated a conserved exonic hox2 enhancer from lamprey that drives segmental expression in rhombomeres 2 and 4. Our results show that coupling of Hox gene expression to segmentation of the hindbrain is an ancient trait with origin at the base of vertebrates that probably led to the formation of rhombomeric compartments with an underlying Hox code. (paywall)
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