Repurposing of a gill gene regulatory program for outer-ear evolution

• 成果类型: Article
• 署名作者: Thiruppathy, Mathi; Teubner, Lauren; Roberts, Ryan R.; Lasser, Micaela C.; Moscatello, Alessandra; Chen, Ya-Wen; Hochstim, Christian; Ruffins, Seth; Sarkar, Arijita; Tassey, Jade; Evseenko, Denis; Lozito, Thomas P.; Willsey, Helen Rankin; Gillis, J. Andrew; Crump, J. Gage
• 署名单位: University of Southern California; University of California System; University of California San Francisco; New York Medical College; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Children's Hospital Los Angeles; University of Southern California; University of Southern California; Chan Zuckerberg Initiative (CZI); Marine Biological Laboratory - Woods Hole
• 刊物名称: Nature
• ISSN/ISSBN: 0028-2587
• DOI: 10.1038/s41586-024-08577-5
• 发表日期: 2025-03-20
• 关键词: homeobox genes; cartilage; expression; specification; enhancers; distinct; tissues; larynx; sox9

摘要

How new structures emerge during evolution has long fascinated biologists. An example is how the diminutive bones of the mammalian middle ear arose from ancestral fish jawbones1. By contrast, the evolutionary origin of the outer ear, another mammalian innovation, remains a mystery, partly because it is supported by non-mineralized elastic cartilage, which is rarely recovered in fossils. Whether the outer ear arose de novo or through the reuse of ancestral developmental programs has remained 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 the later development of the elastic cartilage. Comparative single-nucleus 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 the transgenic activity of human outer-ear enhancers in gills, and of fish gill enhancers in the outer ear. Furthermore, single-cell multiomics of the cartilaginous book gills of horseshoe crabs reveals a developmental program shared with the distal-less homeobox (DLX)-mediated gill program of vertebrates, with a book-gill distal-less 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.