PUBLICATION
Repurposing of a gill gene regulatory program for outer ear evolution
- Authors
- Thiruppathy, M., Teubner, L., Roberts, R.R., Lasser, M., Moscatello, A., Chen, Y.W., Hochstim, C., Ruffins, S., Sarkar, A., Tassey, J., Evseenko, D., Lozito, T.P., Willsey, H.R., Gillis, J.A., Crump, J.G.
- ID
- ZDB-PUB-250110-9
- Date
- 2025
- Source
- Nature : (Journal)
- Registered Authors
- Crump, Gage DeKoeyer
- Keywords
- none
- MeSH Terms
-
- Animals
- Biological Evolution
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Enhancer Elements, Genetic*/genetics
- Gills*/metabolism
- Humans
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Gene Expression Regulation, Developmental*
- Single-Cell Analysis
- PubMed
- 39788155 Full text @ Nature
Citation
Thiruppathy, M., Teubner, L., Roberts, R.R., Lasser, M., Moscatello, A., Chen, Y.W., Hochstim, C., Ruffins, S., Sarkar, A., Tassey, J., Evseenko, D., Lozito, T.P., Willsey, H.R., Gillis, J.A., Crump, J.G. (2025) Repurposing of a gill gene regulatory program for outer ear evolution. Nature. :.
Abstract
How novel structures emerge during evolution has long fascinated biologists. A dramatic example is how the diminutive bones of the mammalian middle ear arose from ancestral fish jawbones1. In contrast, the evolutionary origin of the outer ear, another mammalian innovation, remains a mystery, in part because it is supported by non-mineralized elastic cartilage rarely recovered in fossils. Whether the outer ear arose de novo or through reuse of ancestral developmental programs is unknown. Here we show that the outer ear shares gene regulatory programs with the gills of fishes and amphibians for both its initial outgrowth and later development of elastic cartilage. Comparative single-nuclei multiomics of the human outer ear and zebrafish gills reveals conserved gene expression and putative enhancers enriched for common transcription factor binding motifs. This is reflected by transgenic activity of human outer ear enhancers in gills, and fish gill enhancers in the outer ear. Further, single-cell multiomics of the cartilaginous book gills of horseshoe crabs reveal a shared DLX-mediated gill program with vertebrates, with a book gill distalless enhancer driving expression in zebrafish gills. We propose that elements of an invertebrate gill program were reutilized in vertebrates to generate first gills and then the outer ear.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping