Hominoid-specific transposable elements reshaped neural crest migration in craniofacial development.

Area of Science:

• Evolutionary biology
• Genomics
• Developmental biology

Background:

• Craniofacial development is crucial for vertebrate evolution, with species-specific traits arising from regulatory network changes.
• Transposable elements (TEs) drive genome evolution, but their specific role in cranial neural crest cells (CNCCs) is not well understood.

Purpose of the Study:

• Investigate the domestication of hominoid-specific TEs (LTR5Hs and SVAs) as enhancers in human CNCC specification.
• Determine the impact of these TEs on craniofacial development and evolution.

Main Methods:

• Utilized human induced pluripotent stem cell (iPSC)-derived CNCCs.
• Identified hominoid-specific TEs functioning as enhancers using CRISPR-interference.
• Performed transcriptional profiling and functional assays to assess CNCC migration and gene expression.

Main Results:

• Discovered ~515 hominoid-specific TEs acting as enhancers in human CNCCs, with ~250 being human-specific (predominantly LTR5Hs).
• These TEs are enriched for CNCC motifs, bound by TWIST1, and exhibit CNCC-specific enhancer activity.
• Repression of these TEs disrupted gene expression, impaired CNCC migration, and normalized human-specific gene expression differences compared to chimpanzees.

Conclusions:

• Young TEs have been domesticated to regulate CNCCs, fine-tuning developmental networks.
• This TE domestication likely contributes to lineage-specific craniofacial evolution in humans.